期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 125, 期 2, 页码 336-346出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.08.031
关键词
Asthma; genome-wide association study; ADRA1B; PRNP; DPP10; African ancestry; ethnicity; polymorphism; genetic association
资金
- National Institutes of Health [HL087699, HL49611, AI50024, AI44840, HL075417, HL072433, AI41040, FS09606, RR03048]
- US Environmental Protection Agency [83213901]
- NIGMS [S06GM08015]
- Wellcome Trust
- Medical Research Council
- French Ministry of Higher Education and Research
- German Ministry of Education and Research (BMBF)
- National Genuine Research Network (NGFN)
- National Institutes of Health (National Human Genome Research Institute and National Heart, Lung, and Blood Institute, G. R. A.)
- European Commission
- Mary Beryl Patch Turnbull Scholar Program
- National Human Genome Research Institute, National Institutes of Health
- National Institutes of Health
- Pfizer
- Centocor
- Novartis
- Centers for Medicine and Medicaid Services
- Genentech
- DFG
- BMBF
- European Union
- GlaxoSmithKline
- Medical Research Council [G0801056B] Funding Source: researchfish
Background: Asthma is a complex disease characterized by striking ethnic disparities not explained entirely by environmental, social, cultural, or economic factors. Of the limited genetic studies performed on populations of African descent, notable differences in susceptibility allele frequencies have been observed. Objectives: We sought to test the hypothesis that some genes might contribute to the profound disparities in asthma. Methods: We performed a genome-wide association study in 2 independent populations of African ancestry (935 African American asthmatic cases and control subjects from the Baltimore-Washington, DC, area and 929 African Caribbean asthmatic subjects and their family members from Barbados) to identify single-nucleotide polymorphisms (SNPs) associated with asthma. Results: A meta-analysis combining these 2 African-ancestry populations yielded 3 SNPs with a combined P value of less than 10(-5) in genes of potential biologic relevance to asthma and allergic disease: rs10515807, mapping to the alpha-1B-adrenergic receptor (ADRA1B) gene on chromosome 5q33 (3.57 x 10(-6)); rs6052761, mapping to the prion-related protein (PRNP) gene on chromosome 20pter-p12 (2.27 x 10(-6)); and rs1435879, mapping to the dipeptidyl peptidase 10 (DPP10) gene on chromosome 2q12.3-q14.2. The generalizability of these findings was tested in family and case-control panels of United Kingdom and German origin, respectively, but none of the associations observed in the African groups were replicated in these European studies. Evidence for association was also examined in 4 additional case-control studies of African Americans; however, none of the SNPs implicated in the discovery population were replicated. Conclusions: This study illustrates the complexity of identifying true associations for a complex and heterogeneous disease, such asthma, in admixed populations, especially populations of African descent. (J Allergy Clin Immunol 2010;125:336-46.)
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