Asthma is a complex disease that is influenced by both genetic and environmental factors. Genes in the IL-4/IL-13 pathway have been extensively studied as candidates for asthma susceptibility. Previously we reported an interaction between exposure to cigarette smoke in infancy and evidence for linkage to the region on chromosome 5q31 that encodes IL-4 and IL-13 in 144 Caucasian families from the CSGA (Colilla et al., AJHG S69:213, 2001). Both of these cytokines share a common receptor alpha-chain, encoded by the IL4RA gene on 16p12. Here we investigate the relationship between cigarette smoke exposure in infancy and 11 polymorphisms in IL4, IL13 and IL4RA in 233 Caucasian trios and 298 Caucasian non-asthmatic controls ascertained by these same four CSGA centers. Probands were stratified by exposure (169 unexposed, 64 exposed) and the data were analyzed using both TDT (trios) and case-control approaches. There was significant nonrandom transmission of IL13 haplotypes to asthmatic children in the unexposed group (p=0.016), and the IL13 gln110 allele was modestly increased in this group compared with controls (p=0.05). No association was present in the exposed group. Furthermore, using a 2-locus TDT, we identified a significant interaction between the IL13 arg110gln and IL4RA polymorphisms (p=0.001), suggesting an interaction between this Th2 cytokine and its receptor. Overall these data highlight the importance of considering both gene-gene and gene-environment interactions in studies of complex diseases, and further implicate these genes in the pathobiology of asthma.
Department, Program, or Center
Thomas H. Gosnell School of Life Sciences (COS)
American Journal of Human Genetics 71N4 Suppl S (2002) 222
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