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IL13 Promoter Polymorphism –1112C/T Modulates the Adverse Effect of Tobacco Smoking on Lung Function

¹ Center for Human Genomics and Department of Medicine and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ² Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina; and ³ School of Public Health, Saint Louis University, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Alireza Sadeghnejad, M.D., Ph.D., Center for Human Genomics and Departments of Medicine and Pediatrics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. E-mail: asadeghn{at}wfubmc.edu

Rationale: Although the duration and amount of cigarette smoking correlate with reduction in pulmonary function, there is still variation among individual responses. IL-13 is involved in pulmonary inflammation, remodeling, and susceptibility to chronic obstructive pulmonary disease (COPD).

Objectives: We investigated whether the relationships between smoking and the lung function measures FEV₁ and FEV₁/FVC ratio are modulated by IL13 polymorphisms.

Methods: Smokers (20 pack-years), aged at least 40 years old (n = 1,073), were genotyped for three single nucleotide polymorphisms (SNPs; –1112C/T [rs1800925], +2044G/A [rs20541, R130Q], and +2525G/A [rs1295685]) in the IL13 gene. Linear, quantile, and logistic regression methods were used to assess the effect of cigarette smoking (pack-years), IL13 polymorphisms, and their interaction on %predicted FEV₁ and FEV₁/FVC ratio. Age, sex, and current smoking status were included as confounders.

Measurements and Main Results: The number of pack-years smoked was associated with a lower value for both %predicted FEV₁ and FEV₁/FVC (P < 0.001).The three SNPs were not associated with lung function measures; however, there was a significant combined effect between smoking and the promoter polymorphism –1112C/T on %predicted FEV₁ (P for interaction < 0.03 for mean %predicted FEV₁ and < 0.0001 for 90th percentile %predicted FEV₁). Every 20–pack-year increment in smoking was associated with a 2.4% reduction in mean %predicted FEV₁ in the common homozygous (CC) or heterozygous (CT) promoter genotypes, and an 8.2% reduction in mean %predicted FEV₁ in minor allele homozygotes (TT, recessive model).

Conclusions: An IL13 polymorphism in the promoter region may modulate the adverse effects of cigarette smoking on pulmonary function in long-term cigarette smokers.

Key Words: interleukin 13 • polymorphism • tobacco smoke • gene–environment interaction

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject There is very limited knowledge about the combined effect of genes and cigarette smoking on lung function. What This Study Adds to the Field An interaction between the –1112C/T variant in the promoter region of the IL13 gene and cigarette smoking may influence lung function in long-term smokers.

 

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