دورية أكاديمية
Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.
العنوان: | Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function. |
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المؤلفون: | Ober C; University of Chicago, Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF Jr, Nicolae DL, Elias JA, Chupp GL |
المصدر: | The New England journal of medicine [N Engl J Med] 2008 Apr 17; Vol. 358 (16), pp. 1682-91. Date of Electronic Publication: 2008 Apr 09. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Boston, Massachusetts Medical Society. |
مواضيع طبية MeSH: | Polymorphism, Single Nucleotide*, Asthma/*genetics , Bronchial Hyperreactivity/*genetics , Glycoproteins/*blood , Glycoproteins/*genetics, Adipokines ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asthma/blood ; Biomarkers/blood ; Bronchial Hyperreactivity/blood ; Case-Control Studies ; Child ; Chitinase-3-Like Protein 1 ; Female ; Founder Effect ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lectins ; Male ; Middle Aged ; Phenotype ; Pulmonary Ventilation/genetics |
مستخلص: | 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=1.1 x 10(-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=1.2 x 10(-5)) and serum YKL-40 levels at birth (in cord-blood specimens) through 5 years of age in the birth cohort (P=8.9 x 10(-3) to 2.5 x 10(-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. (Copyright 2008 Massachusetts Medical Society.) |
التعليقات: | Comment in: N Engl J Med. 2008 Apr 17;358(16):1725-6. (PMID: 18403760) |
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معلومات مُعتمدة: | R01 HL085197-02 United States HL NHLBI NIH HHS; HL81638 United States HL NHLBI NIH HHS; R01 HL066533 United States HL NHLBI NIH HHS; M01 RR000055 United States RR NCRR NIH HHS; HL61879 United States HL NHLBI NIH HHS; HL70831 United States HL NHLBI NIH HHS; U01 HL049596 United States HL NHLBI NIH HHS; R01 HL072414 United States HL NHLBI NIH HHS; M01 RR00055 United States RR NCRR NIH HHS; P50 HL056399 United States HL NHLBI NIH HHS; HL66533 United States HL NHLBI NIH HHS; HL56399 United States HL NHLBI NIH HHS; HL85197 United States HL NHLBI NIH HHS; P50 HL056389 United States HL NHLBI NIH HHS; R01 HL085197 United States HL NHLBI NIH HHS; P01 HL056389 United States HL NHLBI NIH HHS; HL72414 United States HL NHLBI NIH HHS; HL56389 United States HL NHLBI NIH HHS; P01 HL070831 United States HL NHLBI NIH HHS |
المشرفين على المادة: | 0 (Adipokines) 0 (Biomarkers) 0 (CHI3L1 protein, human) 0 (Chitinase-3-Like Protein 1) 0 (Glycoproteins) 0 (Lectins) |
تواريخ الأحداث: | Date Created: 20080412 Date Completed: 20080422 Latest Revision: 20220310 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC2629486 |
DOI: | 10.1056/NEJMoa0708801 |
PMID: | 18403759 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1533-4406 |
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DOI: | 10.1056/NEJMoa0708801 |