Association of the TLR4 Asp299Gly polymorphism with lung function in relation to body mass index.

Abstract

Background: Previous studies have shown conflicting results for the association between TLR4 polymorphism (Asp299Gly) and lung function. We investigated the influence of TLR4 Asp299Gly, a polymorphism, on lung function in a community population.

Methods: In 2003, a cross-sectional survey was conducted to assess the respiratory health of residents living in and around the town of Humboldt, Saskatchewan, Canada. There were 2090 adults age 18-79 years who completed a questionnaire that included a medical and smoking history, as well as socio-economic and lifestyle variables. Genetic information and lung function test measurements were available on 1725 subjects (754 males and 971 females) of the 2090 respondents. These subjects were selected for further analysis to investigate the association between TLR4 Asp299Gly genotype and forced expiratory volume in the first second in liters (FEV1), forced vital capacity in liters (FVC), FEV1/FVC ratio, and forced expiratory flow rate in liters/second (FEF25-75). Multivariable linear regression analysis was used to investigate associations.

Results: Adjusted mean values of FEV1 and FVC were significantly different between TLR4 wild type and TLR4 variant groups [Mean +/- S.E.: (TLR4 wild type - FEV1: 3.18 +/- 0.02, FVC: 3.95 +/- 0.03; TLR4 variant - FEV1: 3.31 +/- 0.06, FVC: 4.14 +/- 0.07)]. Based on multivariable regression analysis, we observed that body mass index (BMI) was associated with decreased FEV1/FVC ratio and FEF25-75 in TLR4 variant group but not in wild type group.

Conclusion: BMI may modify the associations of TLR4 Asp299Gly polymorphism with FEV1/FVC ratio and FEF25-75.