Influence of cigarette smoking and inflammatory gene polymorphisms on glycated hemoglobin in the Japanese general population

Objective: Inflammation is closely involved in the development of type 2 diabetes, and cigarette smoking acts as potent inducer of inflammation. We therefore investigated interactions between inflammation-related gene polymorphisms and cigarette smoking on glycated hemoglobin (HbA_1c) in the Japanese general population. Method: We conducted a cross-sectional study using data collected from 2619 Japanese (1274 males and 1345 females) 40-69 years of age who participated in baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study (2005-2008). Eight polymorphisms in seven genes (interleukin [IL]-1β, IL-2, IL-4, IL-8, IL-10, IL-13 and tumor necrosis factor-α) were determined using the Invader assay. The interactions of smoking and gene polymorphisms on HbA_1c levels were analyzed using multiple linear and logistic regression models and analysis of covariance with adjustment for potential confounders. Results: Among the eight polymorphisms, only one significant interaction was detected for IL-1β T-31C (P < 0.0001). Among the subjects carrying TT genotype, current heavy smokers (≥20 cigarettes/day) had higher HbA_1c (5.83 [95% confidence interval 5.67-5.99] %) versus all other smoking status groups (never 5.49 [5.41-5.56] %, former 5.54 [5.43-5.65] %, current moderate [<20 cigarettes/day] 5.50 [5.30-5.69] %), whereas such differences were not observed in the subjects with C allele. The logistic regression analyses regarding high-normal HbA_1c levels showed a similar pattern of results. Conclusion: Smoking status did not interact with any other inflammation-related polymorphisms except for IL-1β T-31C. Heavy smokers harboring the TT genotype of IL-1β T-31C polymorphism show a greater adverse effect of smoking on HbA_1c levels among Japanese middle-aged subjects.