Researchers have identified another region of the genome associated with childhood asthma, a condition that affects more than seven million American kids.

Analysis of DNA from about 1,700 children with asthma and 3,500 controls, all of European ancestry, identified several genetic variations on chromosome 1 associated with the risk of developing asthma.  Many of these same SNPs were then also found to be associated with risk for asthma in a sample of more than 1,600 African American children with asthma and 2,045 controls.  All of the newly identified SNPs are located near the gene that encodes DENND1B, a protein known to be involved in the body’s response to foreign particles.

“Many of these particles are well-known triggers of asthma.  In asthma, patients have an inappropriate immune response in which they develop airway inflammation and overreaction of the airway muscle cells,” explained Hakon Hakonarson, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia and the senior author of the study, in a press release.

The chromosome 1 variations identified by the researchers affected the odds of childhood asthma in different ways depending on ethnicity.  Versions of the SNPs associated with increased risk in African Americans were associated with decreased risk in the European sample.  This is not unusual in genetic studies, and often reflects differences in population history.

One of the most promising SNPs is rs1775456.  In African American children, each copy of the less common G version of this variation was associated with 1.86 times increased odds of asthma.  In children with European ancestry, each G was associated with 0.75 times odds of the condition.  The results were published recently in the New England Journal of Medicine.

(23andMe Complete Edition customers can view their data for rs1775456 using the Browse Raw Data feature.)

Hakonarson suggests that his team’s finding that DENND1B has a genetic link to asthma could lead eventually to the development of new types of treatments.

“Other asthma-related genes remain to be discovered, but finding a way to target this common gene variant [found in the study] could benefit large numbers of children,” he said.

Previous research linked genetic variants on chromosome 17 with the risk for childhood asthma in Europeans.  Some of these studies suggested that these variants have an effect only in children who are exposed to tobacco smoke.  More research will be needed to work out the details, but the importance of chromosome 17 in asthma was further supported by the current study, which replicated the previous findings in addition to identifying the new variants on chromosome 1.

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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“I feel like a fish with no water.”

That’s how the child in the public service announcement featuring a flopping, gasping goldfish describes what it feels like to have an asthma attack. The spot encourages parents of the close to nine million kids who suffer from asthma to take steps to decrease the number of attacks their kids have because, as the announcer says, “even one attack is one too many.”

Both environmental factors – things like mold, pollen, cold air and cigarette smoke — and genetic factors are thought to contribute to childhood asthma, a disease that causes more than 10 million missed days of school and leads to about two million trips to the emergency room each year.

Researchers are beginning to realize that asthma that strikes early in life may be a distinct disease from cases that set in later. In 2007, a genomewide association study linked several related SNPs in a region of chromosome 17 specifically to childhood asthma. New research published online today in the New England Journal of Medicine confirms these genetic findings and adds a new twist: the SNPs have an effect only in kids exposed to tobacco smoke.

(23andMe customers can check their data for one of the chromosome 17 SNPs associated with childhood asthma in Research Reports.)

Bouzigon and colleagues studied several hundred French families and found a number of SNPs linked with asthma on chromosome 17, just as in earlier studies. The SNPs were associated only with asthma that began at age four or younger.

Like previous researchers, Bouzigon et al could not determine exactly how the SNPs are related to childhood asthma risk; but they could clearly show that the variants’ effects are triggered by exposure to tobacco smoke. The researchers found that the overall risk of early-onset asthma was increased at least 1.7-fold for people with two risky copies of any of the SNPs compared to those with none or only one. But when they took smoking into account, they saw that children with two risky copies of any of the SNPs who were also exposed to tobacco in utero, during infancy or both actually had risk at least 2.3-fold higher than those with the more favorable genotypes. The SNPs had no statistically significant effect among children who were not exposed to tobacco smoke early in life.

In an accompanying editorial in NEJM, two researchers not involved in the study — John Holloway and Gerard Koppelman — say that the influence of early life events in the development of asthma is well supported, and that the interaction of genes and tobacco smoke seen by Bouzigon and colleagues “further highlights the detrimental effect of such early life exposure on respiratory health.”

But, say Holloway and Koppelman, the importance of the exact timing of exposure to tobacco smoke is not clear, as Bouzigon et al could not differentiate between prenatal and postnatal exposure.

Although more research will be needed to confirm the results in this new report, Holloway and Koppelman think that as more is learned about how chromosome 17 variants affect asthma risk, this knowledge may help physicians better treat the disease.

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Hutterite girl tests lung function

For people with asthma, chronic inflammation in the lungs narrows airways and makes it difficult to breathe. New research published online this week in the New England Journal of Medicine has found that a version of a SNP in a gene called CHI3L1 can increase a person’s risk of developing the disease.

The CHI3L1 gene encodes a protein called YKL-40 that helps the immune system respond to things like dust mites, cockroaches, fungi, and parasitic worms by triggering inflammation, a central component of asthma. Elevated levels of this protein have been found in patients with the disease.

Researchers led by Carole Ober of the University of Chicago focused their asthma research on SNPs associated with increased blood levels of YKL-40.

The initial studies were carried out in the Hutterites, a genetically isolated religious community in South Dakota. This group provides an ideal community for genetic studies because their family relationships are all known and they share the same environmental conditions.

Blood levels of YKL-40 in the Hutterites were most strongly associated with the SNP rs4950928. In previous studies, the G version of this SNP has been shown to reduce blood levels of the protein by interfering with its production.

Ober et al. found that in the Hutterites, the C version of rs4950928 was associated with higher blood levels of YL-40 and was also significantly associated with asthma.

The researchers confirmed their asthma findings in two other groups with European ancestry, one from Chicago and another from Freiberg, Germany. People with two copies of the C version of rs4950928 had 1.85 times greater odds of having asthma than people with only one copy of the C version or two copies of the G version. About 69% percent of people with European ancestry are estimated to have two copies of the C version.

In a group of six-year-olds from Madison, WI, no association was found between rs4950928 and asthma, although the C version of this SNP was associated with increased blood levels of YKL-40. This may mean that the causes of asthma are different in children younger than six years of age compared to older children and adults.

Ober said that this research could have a significant impact on drug development.

“For some people, if you block YKL-40 you might dramatically reduce the severity of the disease. Knowing the genotype at SNP-131C [rs4950928] might identify those most likely to benefit from such a treatment,” she said.

23andMe customers can view their data for rs4950928 in the Genome Explorer (now called Browse Raw Data).

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