The PPARγ Pro12Ala Polymorphism Is Associated With Edcreased Risk Of Newly Diagnosed Type 2 Diabetes In A Chinese Han Population

BackgroundDiabetes mellitus (DM) is one of the most common chronic diseases, and its prevalence rate shows a significantly rising trend. Diabetes divided into two types mainly: type 1 and type 2, and 90 percents of the diabetic population are type 2 diabetes mellitus (T2DM), which associated with decliningβ-cell function and insulin resistance. Genetic factors play an important role in the incidence of type 2 diabetes. Finding and identifiaction susceptibility genes of T2DM are important implication for primary preventing of T2DM and seerening of high risk individuals.In recent years,it has been generally accepted that the Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) is associated with an decreased risk of Type 2 Diabetes mellitus (T2DM). And the association between PPARΓ2 allele A and Type 2 diabetes has been independently revealed in the research of the Japanese American, Finns, Canadian, Americans, the French, etc.The frequency of allele A has significant differences in varied ethnic groups. According to HapMap data and recent studies, the Pro12Ala polymorphism is in a lower frequency of Asian population, which is almost 20 percent of Caucasians [11, 14], requiring much larger sample size of study population to prove the association。So far, no study has replicated the significant association between PPAR-γ2 gene Pro12Ala polymorphism and type 2 diabetes in a Chinese Han population.ObjectivesWe aimed to determine whether the Pro12Ala polymorphism in PPARγ2 was associated with newly diagnosed T2DM in a Chinese Han population. .MethodsThe study population consisted of 1145 newly-diagnosed T2DM patients consecutively recruited from those attending the outpatient clinics of Department of Endocrinology, Tongji Medical College Hospital and 2001 age- and sex-matched healthy controls with NGT were recruited from an unselected population undergoing a routine health check-up in the same hospital from December, 2004 to November, 2007. T2DM patients met the well-established diagnostic criteria recommended by American diabetes association (ADA) and World Health Organization (WHO) incorporating both fasting plasma glucose (FPG) and 2-h oral glucose tolerance test (OGTT). A standard questionnaire was used to collect information about demography, history of diseases, family history of DM, diet habits, tobacco and alcohol consumption, and physical activity. IR index andβcell function were calculated by homeostasis model assessment (HOMA). Plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were also determined.Results1. The frequency of the allele A carrier was significantly lower in T2DM patients compared to controls, and the odds ratio (OR) was 0.692 (95% CI 0.523 to 0.915, P <0.05), after adjusting for conventional risk factors.2. In stratified analysis, the protective effects associated with the allele A was stronger in subjects who were males, less than 60 years old, overweight, no hypertension and no family history. And the SNP rs1801282 had significant interactions with age, BMI, hypertension and family history (P =0.001, 0.001, 0.001 and 0.002, respectively).3. The protective factor allele A of rs1801282 with no hypertension had a cumulative association with T2DM; the OR for T2DM was 0.346 (95% CI 0.238 to 0.503, P <0.05) for those with all the protective factors as compared with subjects without any of the factors.4. The protective factor allele A of rs1801282 with no family history had a cumulative association with T2DM; the OR for T2DM was 0.464 (95% CI 0.326 to 0.662, P <0.05) for those with all the protective factors as compared with subjects without any of the factors.5. We also found that diabetic subjects carried the allele A had a trend towards higher HOMA-beta,HDL and lower HOMA-IR,BMI,but not reached statistical significance.Conclusions1. The Pro12Ala polymorphism in PPARγ2 is significantly associated with T2DM in Chinese Han Population.2. The Pro12Ala polymorphism in PPARγ2 combined with no Hypertension has a cumulative association with T2DM.3. The Pro12Ala polymorphism in PPARγ2 combined with no Family history has a cumulative association with T2DM.