Matthew J Loza1, Bao-Li Chang. 1. Department of Internal Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA. mloza@wfubmc.edu
Abstract
BACKGROUND: IL4R, the gene encoding the alpha chain of the IL-4 and IL-13 receptors, has received extensive attention as a candidate gene for asthma risk. However, the results from studies testing for associations of the I50V and Q551R IL4R genetic variants are conflicting. OBJECTIVE: We sought to determine the average risk of asthma associated with the I50V and Q551R IL4R variants based on the results of case-control studies reported in the literature. METHODS: Meta-analyses were performed with data from case-control association studies that met specified inclusion criteria (9 and 8 studies for I50V and Q551R, respectively). Random-effects models were used to calculate combined odds ratios (ORs) and significance of associations. Analyses were performed for asthma in general and for subgroups based on the atopy status of the asthma population. RESULTS: The R551 IL4R variant was significantly associated with increased risk of asthma, most notably atopic asthma (combined OR, 1.6; P = .004). Exclusion of the outlier study reporting an OR of less than 1 greatly increased the significance of association (OR, 1.8; P = 3 x 10(-9)). I50V variants were not significantly associated with asthma. CONCLUSIONS: A meta-analysis of results from case-control studies strongly supports the conclusion that the R551 IL4R variant imparts a modest yet significant risk for atopic asthma. CLINICAL IMPLICATIONS: Knowledge that the R551 IL4R variant is associated with increased asthma risk should provide a basis for understanding the heterogeneity of asthma pathogenesis and for pharmacogenetic approaches to treat individuals carrying this variant.
BACKGROUND:IL4R, the gene encoding the alpha chain of the IL-4 and IL-13 receptors, has received extensive attention as a candidate gene for asthma risk. However, the results from studies testing for associations of the I50V and Q551RIL4R genetic variants are conflicting. OBJECTIVE: We sought to determine the average risk of asthma associated with the I50V and Q551RIL4R variants based on the results of case-control studies reported in the literature. METHODS: Meta-analyses were performed with data from case-control association studies that met specified inclusion criteria (9 and 8 studies for I50V and Q551R, respectively). Random-effects models were used to calculate combined odds ratios (ORs) and significance of associations. Analyses were performed for asthma in general and for subgroups based on the atopy status of the asthma population. RESULTS: The R551 IL4R variant was significantly associated with increased risk of asthma, most notably atopic asthma (combined OR, 1.6; P = .004). Exclusion of the outlier study reporting an OR of less than 1 greatly increased the significance of association (OR, 1.8; P = 3 x 10(-9)). I50V variants were not significantly associated with asthma. CONCLUSIONS: A meta-analysis of results from case-control studies strongly supports the conclusion that the R551 IL4R variant imparts a modest yet significant risk for atopic asthma. CLINICAL IMPLICATIONS: Knowledge that the R551 IL4R variant is associated with increased asthma risk should provide a basis for understanding the heterogeneity of asthma pathogenesis and for pharmacogenetic approaches to treat individuals carrying this variant.
Authors: Xiaoguang Sun; Shwu-Fan Ma; Michael S Wade; Carlos Flores; Maria Pino-Yanes; Jaideep Moitra; Carole Ober; Rick Kittles; Aliya N Husain; Jean G Ford; Joe G N Garcia Journal: J Allergy Clin Immunol Date: 2010-07-10 Impact factor: 10.793
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