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American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 379-385, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.4885

Polymorphisms in the IL13, IL13RA1, and IL4RA Genes and Rate of Decline in Lung Function in Smokers

Jian-Qing He, John E. Connett, Nicholas R. Anthonisen and Andrew J. Sandford

UBC McDonald Research Laboratories/iCAPTURE Center, St. Paul's Hospital, Vancouver, British Columbia, Canada; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota; and Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Address correspondence to: Dr. A. J. Sandford, UBC McDonald Research Laboratories/iCAPTURE Center, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. E-mail: asandford{at}mrl.ubc.ca

Targeted expression of interleukin (IL)-13 in the adult murine lung has been shown to cause emphysema. We hypothesized that variants in the IL13, IL13RA1, and IL4RA genes would be associated with an accelerated rate of decline of lung function among smokers. We determined the allele frequencies of five polymorphisms in the IL13, IL13RA1, and IL4RA genes in 588 continuing smokers chosen from the NHLBI Lung Health Study for having the fastest (n = 282) and slowest (n = 306) 5-yr rate of decline of lung function (mean change in FEV1 %predicted/yr = -4.1 and +1.1, respectively). The IL4RA 551RR genotype was associated with rapid decline of lung function (odds ratio, 2.24; P = 0.043). However, none of the other four polymorphisms was associated with rate of decline in lung function. The association of 551RR with rapid decline of lung function became more significant in subjects who also had either the IL13 130RR or –1112TT genotypes. However, because multiple comparisons were made and only a few individuals had the 551RR genotype, these associations may represent type 1 error. Haplotypes consisting of alleles from the IL13 polymorphisms or from the IL4RA polymorphisms were not associated with rate of decline in lung function in smokers.

Abbreviations: airway hyperresponsiveness, AHR • chronic obstructive pulmonary disease, COPD • interleukin, IL • single nucleotide polymorphism, SNP




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