TY - JOUR
T1 - Ethnicity-specific gene-gene interaction between IL-13 and IL-4Rα among African Americans with asthma
AU - Battle, Natalie C.
AU - Choudhry, Shweta
AU - Tsai, Hui Ju
AU - Eng, Celeste
AU - Kumar, Gunjan
AU - Beckman, Kenneth B.
AU - Naqvi, Mariam
AU - Meade, Kelley
AU - Watson, H. George
AU - LeNoir, Michael
AU - Burchard, Esteban González
PY - 2007/5/1
Y1 - 2007/5/1
N2 - Rationale: Genes in the interleukin (IL)-4/IL-13/IL-4Rα 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-4Rα gene-gene interactions that are associated with asthma in African Americans. Methods: Eighteen single-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4Rα 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-4Rα 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-4Rα 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-4Rα (A+4679G) SNPs for baseline lung function among African-American subjects with asthma. Conclusions: Gene-gene interaction between the IL-13 and IL-4Rα genes may play an important role in asthma among African Americans.
AB - Rationale: Genes in the interleukin (IL)-4/IL-13/IL-4Rα 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-4Rα gene-gene interactions that are associated with asthma in African Americans. Methods: Eighteen single-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4Rα 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-4Rα 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-4Rα 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-4Rα (A+4679G) SNPs for baseline lung function among African-American subjects with asthma. Conclusions: Gene-gene interaction between the IL-13 and IL-4Rα genes may play an important role in asthma among African Americans.
KW - African Americans
KW - Asthma
KW - Gene-gene interaction
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U2 - 10.1164/rccm.200607-992OC
DO - 10.1164/rccm.200607-992OC
M3 - Article
C2 - 17303794
AN - SCOPUS:34247623558
SN - 1073-449X
VL - 175
SP - 881
EP - 887
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 9
ER -