Ethnicity-specific gene-gene interaction between IL-13 and IL-4Ralpha among African Americans with asthma.
BACKGROUND
Genes in the interleukin (IL)-4/IL-13/IL-4Ralpha 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.


OBJECTIVE
To determine whether there are IL-4/IL-13 and IL-4Ralpha gene-gene interactions that are associated with asthma in African Americans.


METHODS
Eighteen single-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4Ralpha 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.


RESULTS
We identified 94 SNPs in IL-4, IL-13, and IL-4Ralpha 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-4Ralpha 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-4Ralpha (A+4679G) SNPs for baseline lung function among African-American subjects with asthma.


CONCLUSIONS
Gene-gene interaction between the IL-13 and IL-4Ralpha genes may play an important role in asthma among African Americans.
Battle
Natalie C
NC
University of California, San Francisco, San Francisco, CA 94143-2911, USA.
Choudhry
Shweta
S
Tsai
Hui-Ju
HJ
Eng
Celeste
C
Kumar
Gunjan
G
Beckman
Kenneth B
KB
Naqvi
Mariam
M
Meade
Kelley
K
Watson
H George
HG
Lenoir
Michael
M
Burchard
Esteban González
EG
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4