Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 175, Issue 9, Pages 881-887Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200607-992OC
Keywords
asthma; African Americans; gene-gene interaction
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Funding
- NCRR NIH HHS [M01 RR01271] Funding Source: Medline
- NHLBI NIH HHS [K23 HL04464, HL07185, HL078885] Funding Source: Medline
- NIGMS NIH HHS [GM61390] Funding Source: Medline
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Rationale: Genes in the interleukin (IL)-4/IL-13/IL-4R alpha pathway have been shown to be associated with asthma and related phenotypes in some populations, but not in others. Furthermore, interaction between these genes has been shown to affect asthma in white and Chinese populations. Objectives: To determine whether there are IL-4/IL-13 and IL-4R alpha gene-gene interactions that are associated with asthma in African Americans. Methods: Eighteen sing le-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4R alpha genes were genotyped in 264 African Americans with asthma and 176 healthy control subjects. We tested the SNPs for genetic associations and gene-gene interactions with asthma, baseline lung function, bronchodilator drug response, and total serum IgE levels. Measurements and Main Results: We identified 94 SNPs in IL-4, IL-13, and IL-4R alpha genes by directly sequencing these genes in 24 African-American subjects with asthma. Seventeen SNPs were analyzed for association with asthma and related phenotypes. We found no evidence of association in the IL-4 gene. One SNP in the IL-13 gene (A-646G, rs2069743) and two SNPs in the IL-4Ra gene (A+4679G, rs1805010, and C+22656T, rs1805015) showed association with lung function (both baseline and post-bronchodilator). Although the association between individual SNPs and asthma-related phenotypes differed from previous studies performed in white and Chinese populations, significant gene-gene interaction was found between the IL-13 (A-646G) and IL-4R alpha (A+4679G) SNPs for baseline lung function among African-American subjects with asthma. Conclusions: Gene-gene interaction between the IL-13 and IL-4R alpha. genes may play an important role in asthma among African Americans.
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