title: Interaction between heavy smoking and CYP2A6 genotypes on type 2 diabetes and its possible pathways.
abstract: OBJECTIVE
  To explore the interactions between smoking and CYP2A6 genotypes on type 2 diabetes (T2DM) as well as potential pathways for smoking in causing T2DM.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  A total of 1344 smokers with complete data from a community-based T2DM survey in Guangzhou and Zhuhai of China from July 2006 to June 2007 were interviewed with a structured questionnaire about socio-demographic status and daily cigarette consumption. Serum glucose, insulin, and cotinine were measured after an overnight fast. Subjects were genotyped for CYP2A6 and classified, according to genotype, into normal, intermediate, slow, or poor nicotine metabolizers based on prior knowledge of CYP2A6 allele associations with nicotine C-oxidation rate. Abdominal obesity was defined as a waist-to-hip ratio ≥0.90 for males or ≥0.85 for females. Type 2 diabetic patients (n=154) were diagnosed according to WHO 1999 criteria. Chi-square tests, multivariate logistic regression models, and a structural equation model were used in this study.
  
  
  RESULTS
  Multivariate analysis indicated that, compared with light smoking, heavy smoking significantly increased the risk of T2DM (odds ratio (OR)=1.75, 95% CI=1.01-3.05). There were significant interactions between heavy smoking and slow CYP2A6 (OR=5.12, 95% CI=1.08-24.23) and poor CYP2A6 metabolizer genotypes (OR=8.54, 95% CI=1.28-57.02) on T2DM. Structural equation modeling indicated that CYP2A6 moderation of smoking quantity risk on T2DM was mediated by the effects on serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.
  
  
  CONCLUSIONS
  Heavy smoking was significantly associated with T2DM, and this association was moderated by CYP2A6 genotype and mediated by serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Road 2, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Chen
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Ling
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D065637:Cytochrome P-450 CYP2A6; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006306:Health Surveys / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6