IL13 promoter polymorphism 1112C/T modulates the adverse effect of tobacco smoking on lung function.
BACKGROUND
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).


OBJECTIVE
We investigated whether the relationships between smoking and the lung function measures FEV(1) and FEV(1)/FVC ratio are modulated by IL13 polymorphisms.


METHODS
Smokers (>or=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 FEV(1) and FEV(1)/FVC ratio. Age, sex, and current smoking status were included as confounders.


RESULTS
The number of pack-years smoked was associated with a lower value for both %predicted FEV(1) and FEV(1)/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 FEV(1) (P for interaction < 0.03 for mean %predicted FEV(1) and < 0.0001 for 90th percentile %predicted FEV(1)). Every 20-pack-year increment in smoking was associated with a 2.4% reduction in mean %predicted FEV(1) in the common homozygous (CC) or heterozygous (CT) promoter genotypes, and an 8.2% reduction in mean %predicted FEV(1) 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.
Sadeghnejad
Alireza
A
Center for Human Genomics and Department of Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. asadeghn@wfubmc.edu
Meyers
Deborah A
DA
Bottai
Matteo
M
Sterling
David A
DA
Bleecker
Eugene R
ER
Ohar
Jill A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000453:epidemiology / Q000503:physiopathology*; D014797:Vital Capacity / Q000235:genetics* / Q000502:physiology
D018793:Interleukin-13