More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. Scientists know that many of the characteristic symptoms of Parkinson’s — tremors, rigid muscles and movement problems — can be traced back to the loss of dopamine-producing brain cells.  But what researchers don’t fully understand is why these cells are damaged in the first place.

For most cases of Parkinson’s, the brain cell damage is probably the result of  complex interactions between multiple genetic and environmental factors.  Despite years of work, however, hardly any of these factors are known.  But now two research groups have identified several genetic variants associated with the risk of Parkinson’s in Asian and Caucasian populations.  Their results were published online this week in the journal Nature Genetics.

One group, led by Wataru Satake, analyzed the DNA of 2,011 Japanese people with Parkinson’s disease and 18,381 controls.  The other group, made up of U.S. and German researchers (Simón-Sánchez et al.), looked at the genetics of 5,074 Caucasians with Parkinson’s and 8,551 without the disease.

Common variations in and around two genes previously associated with rare familial forms of Parkinson’s disease, SNCA and LRRK2, were associated with the risk for Parkinson’s in the Japanese study.  In the Caucasian study, the association with SNCA was strong, but the evidence for an association between Parkinson’s and common variation near LRRK2 was only suggestive.  Given that the association of mutations in this gene with familial forms of Parkinson’s is so strong, Simón-Sánchez et al. nevertheless think that there truly is a role for SNPs near this gene in non-familial forms of the disease.

(See the table at the end of this post information on all SNPs.)

Satake et al. also found that variations in a region of the genome not previously linked to Parkinson’s disease could affect risk for the disease.  This region of chromosome 1 contains several genes, and it is not yet clear which one might be involved in Parkinson’s.  Satake et al. named the region PARK16.  After comparing their data, the U.S./German group also found a link between Parkinson’s disease and the PARK16 region.

A SNP in the BST1 gene was associated with increased risk for Parkinson’s in the Japanese sample, but did not show any link to the disease in the Caucasian sample.  The risk version of this SNP, however, is found at very low levels in Caucasians.  This may have been why Simón-Sánchez et al. were unable to pick it up in their analysis.

Finally, a SNP in the MAPT gene, which has also been associated with familial forms of Parkinson’s, was associated with disease risk in the Caucasian sample, but not in the Japanese.

Work to find common genetic variations affecting the risk for Parkinson’s will no doubt continue as researchers try to identify all of the puzzle pieces relevant to this devastating disease and how they fit together.

“A further increase in the number and size of cohorts for [genomewide association studies] in [Parkinson's disease] will likely reveal additional common genetic risk loci and these, in turn will improve understanding and, ultimately, treatment of this devastating disorder,” conclude Simón-Sánchez et al.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Although variations in the some of the same genes were found in both the Caucasian and Japanese samples, the same SNPs often do not apply to the different populations. People looking up their own data should use the SNPs listed for the ethnicity they identify most closely with.

*Risk version is more common version of SNP.
**Results did not meet strict cut offs for statistical significance, but researchers suggest the associations are nonetheless real.

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Cisplatin, a cancer chemotherapy drug first approved by the FDA in 1978, revolutionized the treatment of many types of cancer.  Despite its effectiveness, in many cases doctors are forced to reduce the drug’s dose, or abandon it altogether, due to serious side effects on patients’ hearing.

Between 10-25% of adults and up to 60% of children being treated with cisplatin suffer from severe, permanent hearing loss in both ears. This is particularly damaging in kids, because even mild hearing loss can negatively impact learning and social development.

Researchers have suggested that genetic variants that affect the metabolism of cisplatin might explain why some people are susceptible to drug-induced hearing loss, while other patients receiving similar doses are not.  A new report, published online this week in the journal Nature Genetics, has identified variants in two genes that appear to greatly increase the risk of cisplatin-induced hearing loss.  Although the study is a small one, if replicated these findings could one day help doctors make better decisions about how to prescribe cipslatin.

A team led by Colin Ross from the University of British Columbia analyzed the DNA of 162 children (mostly of European ancestry) treated with cisplatin, focusing their search for genetic variants associated with drug-induced hearing loss on 220 genes known to be involved in the absorption, distribution, metabolism and elimination of medications and their breakdown products.

The variants with the largest effects were found in the TPMT gene.  For example, having one or two Cs at rs1142345 increased the odds of cisplatin-induced hearing loss by 10.51 times, although this result was not statistically significant once the researchers adjusted their data to account for the number of SNPs investigated.

(A larger and statistically significant effect was seen with closely related TPMT SNP, rs12201199, that 23andMe does not currently provide data for.  23andMe customers can use the links in this post to check their data using the Browse Raw Data feature.)

Rs1142345, as well as other variants that reduce the function of the TPMT enzyme, have been associated with adverse reactions to a class of drugs called thiopurines that are used as chemotherapy agents and immune system suppressants.

A second SNP associated with cisplatin-induced hearing was rs9332377 in the COMT gene.  Having one or two Ts at this SNP increased the odds of hearing loss by 5.52 times.  This result was also not statistically significant after adjusting the data.

Other variations in the COMT gene have been associated with a variety of traits, including pain sensitivity, willingness to explore new options, recovery from heart surgery, anxiety, and decreased breast cancer risk in tea drinkers.

None of the SNPs identified in this study were associated with hearing loss in children not treated with cisplatin, suggesting that their effect is specific for drug-induced hearing loss.

“These findings suggest that it may be possible identify individuals at higher risk of cisplatin otoxicity [hearing loss] based on genotype, which would improve counseling and treatment options,” the authors write.

They suggest, for example, that children with the riskier versions of the variants identified in this study could be given lower doses of cisplatin or treated instead with carboplatin, a drug that shows nearly similar cancer cure rates as cisplatin, but has less tendency to cause hearing damage.

The authors acknowledge, however, that their results will need to be replicated in independent populations before any decisions about how to use information about these variants in clinical settings can be made.  Research is also needed to understand what, if any, role these variants play in cisplatin-induced hearing loss in adult cancer patients.

Note: Recent studies by other researchers showed that variations in the megalin gene, the GSTP1 gene and the GSTM1 gene were also associated with the risk of cisplatin-induced hearing loss.  The current report from Ross et al. failed to replicate these associations.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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The “stomach flu” isn’t really the flu at all. It’s actually viral gastroenteritis, and its most common cause is a group of viruses called noroviruses. No matter what you call it, the illness is highly contagious and very unpleasant — symptoms include abdominal pain, vomiting, and diarrhea. In close quarters, a norovirus outbreak can quickly spread from person to person, earning the sickness the nickname “cruise ship disease.”

Norovirus is such a problem on cruise ships, in fact, that the Centers for Disease Control and Prevention (CDC) has a Vessel Sanitation Program in place to help control outbreaks.  But the results of a new study, published in this month’s issue of the journal Clinical Infectious Diseases, shows that even stricter criteria for cleanliness may be in order.

Analysis of data from 56 cruise liners evaluated between 2005 and 2008 shows that only 37% of 8,344 toilet area objects (toilet seat, flush handle or button, toilet stall inner handhold, stall inner door handle, restroom inner door handle and baby changing table surfaces) in 273 randomly selected public restrooms were cleaned on a daily basis.  More than half of the ships had overall “thoroughness of disinfection cleaning”  (TDC) scores less than 30%.  Several of these low-scoring ships had nearly perfect CDC sanitation scores.  TDC scores were substantially lower for the three ships that had a norovirus outbreak within four months of evaluation compared to those ships that did not.

Why bring this up in the Spittoon?  A lucky few have less to worry about when planning a seafaring vacation: variation in the FUT2 gene renders some people resistant to the most common strain of norovirus.  Check out the 23andMe Norovirus Resistance Report to learn more!

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New research suggests that your skills behind the wheel may be affected by your genes.

To better understand the effects of a variant in the BDNF gene on motor skills learning, Steven Cramer and colleagues at UC Irvine tested 29 subjects in a driving simulator. Their results, published in the journal Cerebral Cortex, might make you think twice about whom you go on your next road trip with.

Subjects sat in front of a screen with their hands firmly planted at “10 and 2″ on a steering wheel and guided their “car” around a track, attempting to stay centered over a black line. The steering was tuned so that subjects had to begin turning before the screen actually changed.

Over the course of 15 trials, all of the study subjects got better at the driving task. But the seven people who had a T rs6265 improved less than those with two Cs. When subjects returned to the lab four days later for a final lap, everyone had forgotten how to drive the simulator a little bit, but those with a T did worse.

“These people [with a T at rs6265] make more errors from the get-go, and they forget more of what they learned after time away,” Cramer said in a press release.

(23andMe customers can check their data for rs6265 using the Browse Raw Data feature.)

The BDNF protein helps to regulate how nerve cells make new connections and maintain old ones. The T version of rs6265, also known as the Val66Met variant, reduces the amount of BDNF available in the brain and has been linked to impaired learning and memory. Studies have shown that stroke victims with this variant don’t recover as well as those who lack it.

But there may be an upside: the variant seems to have a beneficial effect on cognition in people with Parkinson’s disease, Huntington’s disease, lupus and multiple sclerosis.

“It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”

See Wired Science for more.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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Medco Health Solutions, Inc., announced this week that it will conduct a clinical trial to assess whether clopidogrel bisulfate (Plavix®, Bristol-Myers Squibb and Sanofi-aventis) is just as effective as the newer drug prasugrel (Effient™, Eli Lilly and Company) in people who lack a genetic variation that inhibits their metabolism of clopidogrel. This new research has important implications for both patient safety and health care costs.

Both clopidogrel and prasugrel are anti-platelet medications that reduce the ability of blood to form clots. The drugs are used to reduce the risk of a heart attack and stroke in people who have suffered from a recent cardiovascular event, and in those who have peripheral artery disease, unstable angina or a stent.

Variations in the CYP2C19 gene that prevent clopidogrel from being converted into its active form in the body have been shown to prevent patients from receiving the drug’s full benefit. People with these gene variations who are taking clopidogrel may be at a higher risk for heart attacks, strokes and death from cardiovascular causes than those whose genetics allow them to metabolize the drug.

(Prasugrel is metabolized through a different biological pathway than clopidogrel, and is not affected by CYP2C19 variants.)

23andMe customers can see their data for several important CYP2C19 variations in the ‘Clopidogrel (Plavix®) Efficacy’ Clinical Report.

Medco’s study will assess patients’ rates of nonfatal heart attacks, nonfatal strokes and cardiovascular deaths after six months of treatment with either clopidogrel or prasugrel. Researchers will be looking to see if there is any difference between those patients who are taking clopidogrel, and whose genetics predict that they should be able to metabolize it—and those patients who are taking prasugrel.

“Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment,” said Medco’s chief medical officer Dr. Robert Epstein in a press release.

Former U.S. Secretary of Health and Human Services Michael O. Leavitt was quoted in the Medco press release as saying, “Studies like this are necessary to show how innovation can derive greater value from what we spend on health care.  A simple test can identify a drug’s ability to work for a particular patient or point them to another one that could provide a better outcome. Personalized medicine is the new frontier in making medication safer and more effective. What we learn from this study, and others like it, will save lives and money.”

Patients aren’t the only ones who would save if Medco’s research shows that the soon-to-be generic clopidogrel is an effective choice for them. An Associated Press story notes that generic drugs are more profitable for Medco than higher-priced brand name products.

Comparative effectiveness research has received a lot of attention in the United States health care debate lately.  Some worry that it will result in policies that are not in patients’ best interests.

“We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,” said National Institutes of Health (NIH) director Francis Collins, speaking at a recent American Association for the Advancement of Science forum on personalized medicine.

Collins recommended that genetic factors be included in comparative effectiveness research (as is the case in Medco’s study), to make sure that treatments that work for specific groups of patients are not “lost in the wash by considering everybody equivalent.”

The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) is part of Medco’s “Genetics for Generics” program and is registered with the NIH.

Related Spittoon Posts:
More Evidence that Genetics Can Reduce the Efficacy of Anti-Clotting Medication Clopidogrel
SNPwatch: Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack

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Doctors routinely order the complete blood count (CBC) for their patients because they can learn a lot about a person’s health by measuring the numbers of different types of blood cells in the circulation, their sizes and the ratios between them.

One component of the CBC is usually a measure of the total amount of hemoglobin, the oxygen carrying protein found in red blood cells.  Low levels of hemoglobin can be a sign of nutritional deficiency, autoimmune disease or bone marrow problems, and may result in fatigue, irregular heartbeat and poor growth in children.  Abnormally high levels of hemoglobin can be caused by heart failure, COPD or kidney cancer and are associated with increased risk of stroke.

New research published online in the journal Nature Genetics this week identifies two SNPs that account for a small amount of the variation in hemoglobin levels seen in the population and may help scientists find new ways to treat blood disorders.

John Chambers and colleagues analyzed the DNA from more than 11,000 Europeans in England and Finland and more than 16,000 Indian Asians living in London.  They found rs855791 and rs198846 both impacted hemoglobin levels.

In both the European and Indian study groups, each A at rs855791 and each G at rs198846 led to an approximately 0.1 gram per deciliter (g/dL) decrease in hemoglobin levels. The normal range for hemoglobin levels in adults is 12 to 18 g/dL.

(23andMe does not currently offer data for rs198846.  Customers can use rs1799945 as a proxy for this SNP.  The C version of rs1799945 corresponds to the lower hemoglobin levels G version of rs198846.)

Approximately 25% of the world’s population has hemoglobin levels low enough to be considered anemic.  The World Health Organization has deemed anemia a severe public health problem in India.  Although nutritional iron deficiencies are a large part of the problem in this and other countries with high levels of anemia, it is interesting to note that the versions of rs855791 and rs198846 that lead to lower hemoglobin levels were found at higher frequencies in the Indian study subjects.

Both SNPs identified in this study are in or near genes involved in regulating the body’s iron levels.

Rs198846 is near the HFE gene.  Mutations in this gene cause hereditary hemochromatosis, a condition that can result in iron overload.  The researchers found, however, that the effect of rs198846 is not related to these mutations.

Rs855791 is located in the TMPRSS6 gene.  Mutations in this gene have been shown to cause a serious form of anemia that does not respond to treatment with oral iron supplements.  Chambers says that learning more about how this gene contributes to hemoglobin levels could lead to new treatments for people suffering from chronic hemoglobin problems.

“The enzyme protein produced by the TMPRSS6 gene is a good target for drug development. Designing a drug that enhances TMPRSS6 activity could augment hemoglobin in people such as cancer and kidney failure patients, who suffer from chronically low levels. A different drug that blocked TMPRSS6 enzyme production might bring down high hemoglobin levels,” he said in a statement.

Several other reports published online this week in Nature Genetics (Benyamin et al., Soranzo et al. and Ganesh et al.) also examined genetic contributions to blood traits.  These will be covered later this week here in the Spittoon.  Benyamin et al. and Ganesh et al. also both found evidence for an association between rs855791 and hemoglobin concentration.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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How do you get three billion pairs of As, Cs, Ts and Gs—about six feet worth of DNA—into the nucleus of a tiny cell?

Most students of biology would answer by saying that this is accomplished by tightly coiling up the DNA.

Oh yeah?  Well, how is it coiled?

As cells perform different functions and respond to different environmental signals, proteins that help turn genes on and off need to quickly gain access to different parts of the genome.  That means DNA needs to be arranged in such a way that it won’t get all tangled up.  Packing DNA like luggage at the end of a vacation, with everything smashed together and shoved in any which way, just won’t cut it.

Using a new technique called “Hi-C,” researchers at Harvard, MIT and the University of Massachusetts appear to have solved the riddle. Their results, published today in the journal Science, show that nature has devised quite an elegant storage solution.

Equilibrium (top) and fractal (bottom) globules. Nearby regions on a chain of DNA are indicated using similar colors. The equilibrium globule is highly entangled; regions nearby along the chain are far apart in 3D. In the fractal globule, regions nearby along the chain are also nearby in 3D. Images: Leonid A. Mirny and Maxim Imakaev

The scientists first treated cells with formaldehyde to freeze the DNA in place.  They then used enzymes to break the DNA apart and put it back together in a different configuration.  A final step of sequencing allowed them to identify pieces of DNA that are naturally close together in the nucleus.

“We made a fantastic three-dimensional jigsaw puzzle and then, with a computer, solved the puzzle,” said co-first author Nynke van Berkum in a statement.

Two important aspects of DNA organization emerged.  First, there are two main compartments in the nucleus – one for DNA that is in use and one that acts as a storage facility for unneeded sequences.

“Cells cleverly separate the most active genes into their own special neighborhood, to make it easier for proteins and other regulators to reach them,” said one of the paper’s senior authors, Job Dekker of UMass Medical School, in a statement.

The other striking aspect of the nucleus is that chromosomes appear to be folded up into an arrangement called a fractal globule, which the authors described as a “beads-on-a-string” configuration.  Multiple rounds of “crumpling” of the DNA into beads leads to a “globule-of-globules-of-globules.”

Previous models suggested that DNA was in a more random arrangement called an equilibrium globule.  This configuration, however, is known to be prone to dense knotting.  Fractal globules are knot-free.

Image Source: Harvard School of Engineering and Applied Sciences

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The princes of early 20th century Europe had a problem.  The source of their wealth and power — the royal blood coursing through their veins — could also sentence them to an early death.

A mutation that spontaneously arose in the DNA of Britain’s Queen Victoria doomed many of her male descendents to the bleeding disorder known as hemophilia. The mutation is known to have been on one of her X chromosomes, but because it didn’t last beyond the fourth generation scientists have never been able to tell which type of hemophilia plagued the princes of Europe.  Now researchers studying the remains of the Romanovs, the Russian royals killed at the start of the Bolshevik revolution, appear to have finally identified the “royal disease.”

Empress Alexandra, wife of Emperor Nicholas and granddaughter of Queen Victoria, is known to have been a carrier for the royal hemophilia mutation because her son, Crown Prince Alexei, was afflicted with the disease. By analyzing the X chromosome DNA in Alexandra’s remains, Evgeny Rogaev and colleagues uncovered a tiny, single-base DNA change in the gene that encodes factor IX, an essential blood clotting protein.

This result, published online today in Science Express, indicates that the royal families of Europe suffered from hemophilia B.  This form of the disease is about seven times less common than classic hemophilia (also called hemophilia A), which is caused by mutations in the gene that encodes another clotting protein, factor VIII.

As expected, when the researchers looked at Alexei’s DNA, they found that his X chromosome contained the factor IX mutation.  DNA from remains presumed to be from Grand Duchess Anastasia also showed evidence of this factor IX mutation, meaning that like her mother she was a carrier for hemophilia.  Had this young girl really escaped execution, as was rumored for many years, any sons she had would have each had a 50% chance of continuing on the tradition of the royal disease.

Image:Permission of the State Archives of the Russian Federation

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In the United States, prostate cancer affects about one in every six men.  Genomewide association studies aimed at finding common genetic variants associated with this common disease have been particularly successful. More than a dozen SNPs have been associated with prostate cancer, but researchers calculate that these variants represent only a tiny fraction of the genetic component of the disease.

To fill in the genetic gaps, researchers are turning to studies that include larger numbers of participants than ever before.  The hard work is paying off, as can be seen in four recent reports published in the journal Nature Genetics.  These analyses, based on the DNA of tens of thousands of men, have added at least 12 new variants to the roster of prostate cancer-associated SNPs.

One of the most striking features of these new studies is that they have identified two new SNPs on chromosome eight in a region known as 8q24.  Three other variants in this same region have already been linked to prostate cancer in both African American and European samples.  Other SNPs in the 8q24 region have been associated with breast, bladder and colorectal cancer.

(The new 8q24 SNPs as well as the others associated with prostate cancer are detailed in a table at the end of this post.)

The bounty of cancer-related SNPs in the 8q24 region is puzzling to scientists because there are no actual genes in this stretch of DNA.  The closest gene, MYC, is known to be involved in cancer, but so far there is no evidence that the cancer-associated 8q24 SNPs are affecting MYC. Future research will hopefully identify what these SNPs are doing and how they affect cancer risk.

Even though prostate cancer genomewide association studies have been fruitful, critics such as John Witte of UCSF argue that the findings may not be clinically useful (read his February Nature Genetics review of prostate cancer genomics here).

But that doesn’t mean that looking for variants associated with prostate cancer should be abandoned.  Finding SNPs associated with the disease could lead scientists to new treatments.

There is also the possibility of finding variants that don’t just predict whether someone is at risk for prostate cancer, but whether they are at risk for a particularly aggressive form of the disease. This could help doctors discriminate between those men whose cancers require immediate treatment and those who can avoid the side effects of surgery and radiation in favor of “watchful waiting.”

“There is clear clinical utility in identifying markers that can distinguish which prostate tumors will progress rapidly and be life-threatening versus those that are relatively latent and may not substantively impact a man’s health,” Witte writes.

As has been the case with most other studies looking for genetic variants associated with prostate cancer, none of the four new studies found an association between the identified SNPs and disease severity. Scientists have suggested that this indicates the studies are mainly finding variations associated with increased risk for the initiation of cancer. To find disease aggression-associated variants, more large studies will be needed, and researchers will need to focus on SNPs correlated with disease recurrence following treatment and/or mortality instead of just presence or absence of disease.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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Unlike the flu virus, which the body is generally able to fight off completely, infection with hepatitis C is often chronic.  That means for most of the three to four million people worldwide who are newly infected each year the virus will persist in the body, where it greatly increases risk for chronic liver diseases including cirrhosis and cancer. The only treatment currently available — an almost year long course of drugs — often causes severe side-effects. Worse yet, it fails in about half of all patients.

Last month, a study published online in the journal Nature showed that DNA variations in and around the IL28B gene influence whether a person chronically infected with the hepatitis C virus will fully respond to the standard treatment regimen. Now three new reports further support the importance of IL28B variations in the body’s response to hepatitis C, a finding that has implications for the future of hepatitis treatment and drug development.

An Australian group headed up by Vijayaprakash Suppiah analyzed the DNA of more than 800 people with European ancestry from Australia, the UK, Germany and Italy infected with hepatitis C.  They found that having one or two copies of the less-common G version of rs8099917, a SNP near the IL28B gene, doubled the odds that a person would fail to have a sustained response to treatment.

A group headed up by Yasuhito Tanaka studied 326 Japanese hepatitis C patients and also found that rs8099917 predicts whether or not a person will respond to treatment.  In this population, however, the effect was much greater.  Carrying a G increased the odds of treatment failure by at least twelve times.

“This SNP has such a strong association with response that, in combination with other parameters, genotyping it and other genetic variants should be a useful part of  clinical management,” write Suppiah et al., who along with Tanaka et al. published their results online this week in the journal Nature Genetics.

Another study, this one published online in Nature, found that variation near IL28B might be part of what allows a minority of people infected with hepatitis C to clear the virus naturally, without any treatment.

David Thomas and colleagues found that individuals with European or African ancestry were about three times more likely to spontaneously clear a hepatitis C infection if they carried two copies of the C version of rs12979860 than if they had CT or TT at this SNP.

Twenty-eight percent of the people with the CT or TT genotypes were able to fight off their hepatitis C infection without treatment, a number very close to the population average.  But 53% of those with the CC genotype were able to become naturally virus-free.

In a commentary published in Nature, Shawn Iadonato and Michael Katze express doubts about the importance of these new discoveries.

“Although these findings raise the tantalizing prospect of a more personalized approach to treating [hepatitis C] by tailoring treatment to patients who are most likely to benefit, the reality is more sobering,” they write.

Iadonato and Katze worry that testing for IL28B variations would not provide doctors with a straightforward yes-or-no answer to the question of whether a patient will respond to hepatitis C treatment.  This is because not all carriers of the advantageous versions of the variants clear the virus, nor do all patients lacking them fail to benefit from treatment.  Furthermore, they point out, there is currently no alternative hepatitis C treatment available.

What they do not consider, however, is how this new research may help change that. In a separate commentary in Nature Genetics, Thomas O’Brien suggests that the current findings could increase the interest in developing hepatitis therapies based on the protein encoded by IL28B, interferon-λ3.  He notes that an early clinical trial testing the effects of a related protein, interferon-λ1, has already had some success.  And certain properties of interferon-λs may cause them to have fewer side effects than current treatments.

O’Brien is still cautious about the findings linking IL28B variations to hepatitis C treatment response.  He says that more research in this area is needed in diverse populations and in people infected with different forms of hepatitis C.  He also stresses that researchers need to consider how these genetic findings fit in with other factors that affect treatment response, including age and gender.

Overall, however, his view is optimistic.  He concludes: “With these caveats, predictive models of HCV treatment response hold the potential to inform treatment decisions for millions of patients who are infected with HCV.”

(Rs12979860 was also described in the original paper linking IL28B to hepatitis C.  23andMe does not currently provide data for this SNP.  As pointed out in the previous Spittoon post on this topic, rs12980275 is very near to this SNP.  The A version of rs12980275 usually corresponds to the C version of rs12979860.  The other SNP discussed in this post, rs8099917, is located close to both rs12979860 and rs12980275.  23andMe customers can look up their data for rs8099917 using the Browse Raw Data feature.  Keep in mind that because all of these SNPs are so closely linked to each other, they are all probably representing the same effect.  More research will be needed to zero in on the exact variation(s) that are important for hepatitis C.)

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Map: PhilippN

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