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

Alireza Sadeghnejad, Deborah A. Meyers, Matteo Bottai, David Sterling, Eugene R. Bleecker, Jill A. Ohar

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume176
Issue number8
DOIs
StatePublished - 15 Oct 2007

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Interleukin-13
Smoking
Lung
Single Nucleotide Polymorphism
Homozygote
Genetic Promoter Regions
Tobacco Products
Chronic Obstructive Pulmonary Disease
Linear Models
Pneumonia
Logistic Models
Alleles
Genotype
Genes

Keywords

  • Gene-environment interaction
  • Interleukin 13
  • Polymorphism
  • Tobacco smoke

Cite this

Sadeghnejad, Alireza ; Meyers, Deborah A. ; Bottai, Matteo ; Sterling, David ; Bleecker, Eugene R. ; Ohar, Jill A. / IL13 promoter polymorphism -1112C/T modulates the adverse effect of tobacco smoking on lung function. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 176, No. 8. pp. 748-752.
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abstract = "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.",
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IL13 promoter polymorphism -1112C/T modulates the adverse effect of tobacco smoking on lung function. / Sadeghnejad, Alireza; Meyers, Deborah A.; Bottai, Matteo; Sterling, David; Bleecker, Eugene R.; Ohar, Jill A.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 8, 15.10.2007, p. 748-752.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - IL13 promoter polymorphism -1112C/T modulates the adverse effect of tobacco smoking on lung function

AU - Sadeghnejad, Alireza

AU - Meyers, Deborah A.

AU - Bottai, Matteo

AU - Sterling, David

AU - Bleecker, Eugene R.

AU - Ohar, Jill A.

PY - 2007/10/15

Y1 - 2007/10/15

N2 - 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.

AB - 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.

KW - Gene-environment interaction

KW - Interleukin 13

KW - Polymorphism

KW - Tobacco smoke

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U2 - 10.1164/rccm.200704-543OC

DO - 10.1164/rccm.200704-543OC

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JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

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