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【medical-news】YKL40-基因和哮喘
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.
by Moffatt, M. F.
ABSTRACT
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 (–131CG) 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.
Source Information
From the University of Chicago, Chicago (C.O., Z.T., Y.S., L.P., R.N., S.R., L.A.L., D.L.N.); the University of Wisconsin, Madison (J.E.G., R.F.L.); Yale University School of Medicine, New Haven, CT (J.D.P., J.A.E., G.L.C.); the University of South Dakota Medical School, Sioux Falls (R.R.P.); and the University of Freiburg, Freiburg, Germany (A.H., K.A.D.).
Drs. Elias and Chupp contributed equally to this article.
This article (10.1056/NEJMoa0708801) was published at www.nejm.org on April 9, 2008.
Address reprint requests to Dr. Ober at the Department of Human Genetics, 920 E. 58th St., University of Chicago, Chicago, IL 60637, or at c-ober@genetics.uchicago.edu.
摘要
http://content.nejm.org/cgi/content/short/358/16/1682
全文
http://content.nejm.org/cgi/content/full/358/16/1682 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Effect of Variation in CHI3L1 on Serum YKL-40 Level, Risk of Asthma, and Lung Function
CHI3L1基因变异对血清YKL-40 水平，哮喘风险和肺功能的影响
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.
背景：类几丁质酶蛋白YKL-40参与炎症和组织重塑。我们最近发现哮喘患者血清中的YKL-40水平增加，并且，血液中YKL-40的水平与哮喘的严重程度、患者气管壁的厚度和肺功能有关。我们猜测单核苷酸多态性(single nucleotide polymorphism) SNPs可影响YKL-40水平，从而影响哮喘的状态和肺功能。
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[标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-01-09 17:14
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