Our SNPwatch posts here at The Spittoon are one of our most exciting features. They give our customers the opportunity to connect their genetic data to the newest discoveries, often within just hours of a study’s publication.

Looking ahead to 2009, we can only begin to imagine the exciting discoveries that will be made in genetics. In the meantime, here are a few of our favorite SNPwatches from 2008:

SNPs That Affect Drug Response
We reported on several studies this year that showed the importance of genetic variations in determining how different people react to certain medications.

• A report in Nature Genetics showed that some women with a particular version of a SNP in the NQO1 are less likely to survive breast cancer after treatment with the commonly used chemotherapeutic epirubicin.
• A study by the SEARCH Collaborative Group found that a version of one SNP is associated with an increased risk for myopathy (muscle pain and/or weakness) in people taking cholesterol-lowering drugs called statins.
• Mayo clinic researchers found that the weight loss drug sibutramine (Meridia) is effective only in people with specific versions of three different genes.
• And just this month we brought you news of three studies that showed that a genetic variant known to affect the metabolism of the anti-clotting drug clopidogrel (Plavix) also affects heart attack patients’ risk of a second major cardiovascular event.

Shared SNPs
Sometimes multiple conditions strike the same person or run in families. Several studies published this year showed that shared genetic risk factors may be part of the reason why.

• Obesity is a known risk factor for many cancers. Researchers found that a variant of adiponectin, a hormone released by fat cells, can increase the risk of developing colorectal cancer.
• Other researchers found variants that affect the risk of developing both type 1 diabetes and celiac disease, two autoimmune diseases that tend to cluster together. One of these shared variants is also associated with HIV resistance.
• Finally, a report published this month in the Proceedings of the National Academy of Sciences showed that a single genetic variant can make a person prone to greater indulgence in both smoking and drinking.

SNPs Associated with Risk Factors for Disease
Several studies this year looked beyond disease itself and instead found associations between SNPs and traits known to be risk factors for disease.

• One study found an association between several SNPs and fasting plasma glucose, a measure of how well a person’s body can control blood sugar levels – a process that goes awry in diabetes.
• Another research group reported SNPs associated with glycated hemoglobin levels, a measure of long-term blood sugar control and another factor associated with the risk of developing diabetes.
• The findings of three papers published in Nature Genetics roughly doubled the number of SNPs associated with blood levels of cholesterol and triglycerides, important risk factors for cardiovascular disease.
• And finally, in a study that looked at behavior instead of metabolic markers, researchers found that a variant in the FTO gene known to increase the risk for obesity affects food choices in children, pushing them towards foods denser in calories.

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Obesity affects about one out of three adults in the United States. And because obese people are at increased risk of high blood pressure, diabetes, cardiovascular disease and other health problems, many authorities consider it one of the most significant public health problems in the developed world.

Of course diet and exercise are important parts of maintaining a healthy weight, but some people need a little more help. Sibutramine (marketed by Abbott Laboratories as Meridia® in the U.S.) is a drug that creates a feeling of fullness, prevents the decline in metabolic rate usually associated with low calorie diets and causes weight loss, especially when combined with behavioral therapy.

But success with sibutramine is variable – for some people it just doesn’t work. New research, published in the October issue of Gastroenterology, shows that genetic differences might be to blame.

“Our results suggest the genetic make-up of patients could predispose their responsiveness to a drug. This could have important implications for the future of personalized molecular-based or individualized medicine,” said the study’s lead author Dr. Michael Camilleri in a statement.

(A video of Dr. Camilleri describing his research can be found at the end of this post.)

Using a sample of 158 overweight and obese people, researchers at the Mayo Clinic tested the effectiveness of sibutramine therapy compared to placebo over 12 weeks. All participants also received behavioral therapy.

The researchers found that weight and body mass index were significantly reduced in patients taking sibutramine compared to placebo, as was expected from previous research. But upon further inspection of the data, the researchers found that only people with certain versions of three different genes experienced significant weight loss.

People with at least one T at the SNP rs5443, in the GNβ3 gene, had success with sibutramine, losing about 13 pounds. People with at least one T at rs5443 and two Cs at rs1800544, in the α2A gene, lost even more weight – more than 17 pounds on average. The drug had no effect if a person had two Cs at rs5443.

The third genetic marker scientists investigated, known in the scientific literature as 5-HTTLPR, is a stretch of DNA that comes in a long and short form. Only people with one or two copies of the short version of this marker had significant weight loss with sibutramine. 23andMe does not currently give data for this type of variant.

“Genetic variations may help select obese patients who are more likely to experience improved outcome with this treatment. Since the different markers were present in almost 50 percent of patients, inclusion of screening for the genetic markers before prescribing the medication may even be cost-effective from a public health perspective,” Camilleri said.

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