Association Studies Between PPARγ2 Pro12Ala/ACE I/D Polymorphism And Type 2 Diabetes In Hubei Han Chinese

Background:Type 2 diabetes mellitus(T2DM)is a multifactorial,heterogeneous disorder characterized by chronic hyperglycemia resulting from pancreaticβ-cell dysfunction and insulin resistance.T2DM accounts for～90-95%of all diabetes syndromes.The WHO estimates suggest that by 2025 there will be 300 million affected people worldwide.The genetic factor plays the key role in the pathogenesis of T2DM. Identification of the susceptibility genes of T2DM would increase understanding of the complex gene-gene and gene-environment interplay causing the disease and will serve to facilitate early diagnosis,treatment and intervention.Objective:To investigate the association of peroxisome-proliferator-activated receptor-γ2(PPARγ2)Pro12Ala and angiotensin-converting enzyme(ACE)gene insertion/deletion(I/D)polymorphisms with T2DM in Hubei Han Chinese.Study designs:Study subjects consist of 337 T2DM patients and 220 healthy controls. Two experimental designs(family-based case-control and unrelated case-control designs) were used.Methods:The Pro12Ala polymorphism of PPARγ2 gene and insertion /deletion(I/D) polymorphism of ACE gene were genotyped by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)methods.All subjects were divided into three groups:all T2DM patients and controls group,family-based case-control group and unrelated case control group.Means between two groups were compared by using independent-sample t-test,whereas paired-sample t-test was used for family-based case control means comparison.The differences of genotype and allelic frequencies between two groups were compared by Chi-square analysis.Logistic regression analysis was performed to evaluate the influence of the genotype and other variables on the risk of T2DM.The differences of clinical characteristics between genotypes were compared by analysis of variance.P＜0.05 was considered statistically significant.All statistical analyses were performed using SPSS11.5 software for windows.Results1.PPARγ2 Pro12Ala polymorphism and T2DMThere was no significant difference of the genotypic and aUelic frequencies of the Pro12Ala polymorphism between T2DM patients and controls group in family-based case control sample.However,the genotypic and allelic frequencies of the Pro12Ala polymorphism between T2DM patients and controls group were significantly different in unrelated case control sample,PA genotype and Ala12 allele's frequencies being higher in the controls group than T2DM patients group(P=0.01).Moreover,there is a trend of weak association between the Pro12Ala polymorphism and T2DM in all subjects sample (genotype,P=0.063;allele,P=0.061).Sub-group analysis on basis of BMI,age and sex showed no differences in genotypic and allelic frequencies of the Prol2Ala polymorphism between T2DM patients and controls group.Logistic regression analysis of all subjects,without or with adjustment for age,sex,hypertension and obesity,showed no association between Prol2Ala polymorphism and T2DM.Multivariate logistic regression analysis of all subjects indicated that the age,weight,abdominal obesity and diastolic blood pressure were independent risk factors for T2DM in the study population.2.ACE I/D polymorphism and T2DM.There was no significant difference in genotypic and allelic frequencies of I/D polymorphism between T2DM patients and controls in all subjects and unrelated case control samples.However,in family-based case control sample the frequency of I allele was significantly higher in T2DM patients than controls group(P=0.013),and theⅡgenotype was marginally significantly associated with T2DM(P=0.054).There was no difference in genotypic and allelic frequencies of the I/D polymorphism between T2DM patients and controls group in the three BMI sub-groups.However,theⅠallele was associated with risk for T2DM in age＜60(P=0.018)and male sub-group(P=0.037). These results indicated that there may be an interaction between the I/D polymorphism and age,sex.Conclusion:The PPARγ2 Pro12Ala and ACE I/D polymorphisms were not major risks of T2DM in Hubei Han Chinese.Age,weight,obesity and hypertension were independent risk factors for T2DM.Additional studies will be required to identify T2DM susceptibility genes in Han Chinese of Hubei.