The Study On The Association Of PPAR?,TCF7L2,KCNJ11,SUR1 Polymorphisms And Environmental Factors With Diabetes Mellitus

[Objective]To find out the dietary patterns,and to research the relationship between environmental factors(especially dietary patterns)and diabetes mellitus among the adult residents of Fujian.To explore the association of gene polymorphisms(TCF7L2,PPAR ?,KCNJ11,and SUR1)related with insulin secretion or resistance and environmental factors with type II diabetes mellitus,and to analyze the gene-gene interaction and gene-environment interaction in the pathogenesis of type II diabetes mellitus.[Methods]1.Cross-sectional study: Multi-stage sampling method were used to survey 6016 resident aged 18 years or older by questionnaire,physical examination and laboratory detection in 10 Disease Surveillance Points in Fujian.Factor analysis was used to identify the dietary patterns,while non-condition logistic regression was applied to analysis relationship between environmental factors(especially dietary patterns)and diabetes.2.Case-control study: we randomly recruited 534 cases from 10 Disease Surveillance Points.All controls were enrolled from non-diabetic population,and were frequency-matched to the cases on gender and age(�5 year).The genotypes of 6polymorphic loci were detected with RFLP.The non-condition logistic regression was used to selected polymorphic loci associated with T2 DM.The MDR model and non-condition logistic regression combined with the principle of crossover analysi analysis were applied to analyze the gene-gene and gene-environment interaction.[Result]1.In diabetes and non-diabetes population,there were statistically significant differences in age,educational level,occupation,DM family history,smoking,drinking,central obesity,BMI,hypertension,dyslipidemia,physical activity,sedentary time and sleep time.2.Factor analysis method obtained four main dietary patterns: animal food pattern,plant food pattern,high-quality protein,and fried food and beverages pattern.3.Risk factors for diabetes included: harmful alcohol drinking,DM family history,hypertension and dyslipidemia.Factor score of plant food pattern at T2 and T3 level was protective factor for diabetes.4.Among adult residents of Fujian,the risk of T2 DM in rs5215 CC genotype carriers and CC+TC genotype carriers were 1.709(95%CI=1.139~2.565)times and 1.363(95%CI=1.028~1.808)times,respectively,than those who carry TT genotype.The risk of T2 DM in rs5215 CC genotype carriers were 1.513(95%CI=1.043~2.195)times than those who carry TT+TC genotype.In the adult male residents,he risk of T2 DM in rs290487 CC genotype carriers were 2.026(95%CI=1.063~3.863)times than those who carry TT+TC genotype.5.In case-control population,mean blood glucose concentration of 2h-OGTT in rs5215 CC genotype carriers higher than rs5215 TT genotype carriers.In patients,mean blood glucose concentration of 2h-OGTT in rs5215 CC+TC genotype carriers higher than rs5215 TT genotype carriers.6.The individual who carry with rs5215 CC+TC genotype and suffer from dyslipidemia(or hypertension,or central obesity,or BMI?24kg/m2)had more risk of T2 DM.The individual who carry with rs1799859 AA+GA genotype and suffer from dyslipidemia also had more risk of T2 DM.The individual who carry with rs5215CC+TC genotype and rs3856806 TT+CT had more risk of T2 DM.There were additive interaction on T2 DM between rs5215 and hypertension.There were negative multiplicative interaction on T2 DM.between rs5215 and rs17998597.The optimal MDR model was the interaction of three factors: central obesity,hypertension and dyslipidemia.The OR of T2 DM was 15.842(95%CI=8.514~29.476) among population who suffer from dyslipidemia and hypertension.The OR of T2 DM was 16.344(95%CI=8.921~29.942)among population who suffer from dyslipidemia and central obesity.The OR of T2 DM was 27.578(95%CI=14.992~50.732)among population who suffer from central obesity,hypertension and dyslipidemia.There were negative multiplicative interaction on T2 DM between central obesity and hypertension.There were additive interaction on T2 DM between dyslipidemia and central obesity.There were additive interaction on T2 DM between dyslipidemia and hypertension.[Conclusion]1.Alcohol drinking,DM family history,hypertension and dyslipidemia were risk factors for diabetes.And plant food pattern at T2 and T3 level was protective factor for diabetes.2.The polymorphism of KCNJ11 rs5215 was associated with the susceptibility of T2 DM in the residents of Fujian.The polymorphism of TCF7L2 rs290487 was associated with the susceptibility of T2 DM in the male residents of Fujian.3.KCNJ11 rs5215 C-allele might be related to blood glucose concentration.4.There were joint effect on T2 DM among rs5215,respectively,with dyslipidemia,hypertension,central obesity,BMI?24kg/m2.There were joint effect on T2 DM between rs1799859 and dyslipidemia.There were joint effect on T2 DM between rs5215 and rs3856806.There were additive interaction on T2 DM between rs5215 and hypertension.There were negative multiplicative interaction on T2 DM between rs5215 and rs1799859.5.There were joint effect on T2 DM among dyslipidemia,hypertension and central obesity.There were additive interaction on T2 DM between dyslipidemia and central obesity.There were additive interaction on T2 DM between dyslipidemia and hypertension.