Association Analysis Of ENPP1 And β2-AR Gene Polymorphisms With Type 2 Diabetes In Han Chinese In Hubei

Background:Diabetes mellitus is a complex metabolic disorder characterized with hyperglycemia,along with a relative deficiency of insulin secretion,a reduced response of target tissues to insulin,resulting in metabolic disorder of carbohydrate,fat and protein. Type 2 diabetes(T2DM)is influenced by both genetic and environmental risk factors such as overweight,obesity,physical inactivity,sedentary behavior and unhealthy dietary habits.Genetic factor plays an important role in the pathogenesis of T2DM.Aim:The purpose of this study is to identify genetic risk factors of T2DM in Han ethnic nationality of Hubei province in China.We examine associations between the K121Q(rs1044498)polymorphism of the pyrophosphatase/phosphodiesterase 1(ENPP1) gene and the C79G(rs1042714)polymorphism ofβ2 adrenergic receptor(β2-AR)and T2DM.Methods:Both the sib-pairs(within-family control)and the random case-control designs are used in this study.The ENPP1 K121Q andβ2-AR C79G polymorphisms were genotyped using both the polymerase chain reaction-restriction fragment length polymorphisms method and fluorescence quantitative polymerase chain reaction analysis in 510 subjects in Hubei province.The Chi-square and logistic regression are used to investigate the relationship between polymorphisms of ENPP1 andβ2-AR and T2DM.Results:(1)The of ENPP1 K121Q(rs1044498)andβ2-AR C79G(rs1042714)genotypic frequencies were in Hardy-Weinberg equilibrium.(2)The frequencies of XQ(KQ+QQ)genotype and 121Q allele in T2DM were significantly higher than those in control in all subjects(genotype:P=0.039;allele: P=0.033)and sib-pairs group(genotype:P=0.014;allele:P=0.008)as well as in the stratified analysis on the basis of BMI(genotype:P=0.032;allele:P=0.02).The logistic regression analysis showed that the XQ genotype was associated with T2DM(before adjusted:OR=1.605,95%CI=1.022-2.521,P=0.04;after adjusted:OR=1.71,95% CI=1.032-2.834,P =0.037).(3)No significant differences in genotypic and allelic frequencies of theβ2-AR C79G polymorphism between cases and controls were detected in all samples(genotype: P=0.577;allele:P=0.273).Logistic regression analysis indicated that theβ2-AR C79G polymorphism was not associated with T2DM(OR=3.167,95%CI=0.482-20.825, P=0.23).(4)There were significant differences in body weight among three genotypes of theβ2-AR C79G in all subjects(P=0.047).Conclusions:(1)ENPP1 K121Q polymorphism is associated with T2DM susceptibility; Genotype XQ and allele Q are risk factors for T2DM in our population.(2)β2-AR C79G polymorphism is not associated with T2DM.(3)β2-AR C79G polymorphism is associated with body weight.