Researchers have isolated a gene that can predict either a greater or reduced risk for developing asthma.
The study found that one variant of the gene, known as CHI3L1, increases the level of YKL-40, a marker for asthma, in the blood. This indicates an increased risk of developing the disease. Another variant of the gene was found to lower levels of YKL-40, indicating a reduced risk.
The researchers cautioned that more studies need to be conducted to identify more genetic factors that impact asthma and other lung disorders. Once this happens, chemists will be able to develop drug treatments for asthma patients.
The study, published Wednesday in the online edition of the New England Journal of Medicine, was conducted by researchers in the United States and Germany.
While a team of scientists from the University of Chicago initially focused the study on Hutterites of South Dakota, a genetically isolated community, the findings were confirmed among non-Hutterite study subjects from Chicago, Madison, Wisc., and Freiberg, Germany.
Since 1994, study author Carole Ober, a professor of human genetics at the University of Chicago Medical Centre, and her colleagues have been analyzing the South Dakota Hutterite colony to identify how genetic factors influence a variety of diseases. The community shares similar genes and descends from about 90 people who can be traced back to the eighteenth century.
"They eat the same food, live off the same allowance and have the same education," Ober said in a statement. "They have similar, but not identical genomes. So the genes that make a difference are easier to detect."
"This is also the most significant genetic discovery based on our years of gathering data on asthma in the Hutterites," Ober added. "This is a group with enormous potential to advance our understanding of the genetic underpinnings of disease. We now have a remarkable collection of data, which we expect will lead us to many more insights."
According to The Asthma Society of Canada, asthma is chronic inflammation of the airways, which causes symptoms such as shortness of breath, chest tightness, coughing and wheezing. There is no known cause or cure.
It is estimated that more than 3 million Canadians have asthma.
Abstract:
Effect of Variation in CHI3L1 on Serum YKL-40 Level, Risk of Asthma, and Lung Function
Carole Ober, Ph.D., Zheng Tan, Ph.D., Ying Sun, M.S., Jennifer D. Possick, M.D., Lin Pan, M.S., Raluca Nicolae, D.D.S., Sadie Radford, Rodney R. Parry, M.D., Andrea Heinzmann, M.D., Klaus A. Deichmann, M.D., Lucille A. Lester, M.D., James E. Gern, M.D., Robert F. Lemanske, Jr., M.D., Dan L. Nicolae, Ph.D., Jack A. Elias, M.D., and Geoffrey L. Chupp, M.D.
Background: The chitinase-like protein YKL-40 is involved in inflammation and tissue remodeling. We recently showed that serum YKL-40 levels were elevated in patients with asthma and were correlated with severity, thickening of the subepithelial basement membrane, and pulmonary function. We hypothesized that single-nucleotide polymorphisms (SNPs) that affect YKL-40 levels also influence asthma status and lung function.
Methods: We carried out a genomewide association study of serum YKL-40 levels in a founder population of European descent, the Hutterites, and then tested for an association between an implicated SNP and asthma and lung function. One associated variant was genotyped in a birth cohort at high risk for asthma, in which YKL-40 levels were measured from birth through 5 years of age, and in two populations of unrelated case patients of European descent with asthma and controls.
Results: A promoter SNP (-131C G) in CHI3L1, the chitinase 3-like 1 gene encoding YKL-40, was associated with elevated serum YKL-40 levels (P=1.1x10-13), asthma (P=0.047), bronchial hyperresponsiveness (P=0.002), and measures of pulmonary function (P=0.046 to 0.002) in the Hutterites. The same SNP could be used to predict the presence of asthma in the two case-control populations (combined P=1.2x10-5) and serum YKL-40 levels at birth (in cord-blood specimens) through 5 years of age in the birth cohort (P=8.9x10-3 to 2.5x10-4).
Conclusions: CHI3L1 is a susceptibility gene for asthma, bronchial hyperresponsiveness, and reduced lung function, and elevated circulating YKL-40 levels are a biomarker for asthma and decline in lung function.
