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Ethnicity-specific Gene–Gene Interaction between IL-13 and IL-4R among African Americans with Asthma

¹ University of California, San Francisco, San Francisco, California; ² Lung Biology Center, UCSF Mission Bay Campus, San Francisco, California; ³ Children's Hospital Oakland Research Institute (CHORI), Oakland, California; ⁴ The James A. Watson Wellness Center, Oakland, California; and ⁵ Bay Area Pediatrics, Oakland, California

Correspondence and requests for reprints should be addressed to Esteban González Burchard, M.D., M.P.H., University of California, San Francisco, San Francisco, CA 94143-2911. E-mail: esteban{at}sfgh.ucsf.edu

Rationale: Genes in the interleukin (IL)-4/IL-13/IL-4R 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 gene–gene interactions that are associated with asthma in African Americans.

Methods: Eighteen single-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4R 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 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-4R 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 (A+4679G) SNPs for baseline lung function among African-American subjects with asthma.

Conclusions: Gene–gene interaction between the IL-13 and IL-4R genes may play an important role in asthma among African Americans.

Key Words: asthma • African Americans • gene–gene interaction

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject IL-4, IL-13, and IL-4R have been associated with asthma-related phenotypes in other populations, but have not been thoroughly studied in African Americans. What This Study Adds to the Field Gene–gene interaction between the IL-13 and IL-4R genes may play an important role in asthma among African Americans.

 

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