Association Of Polymorphism Of LRP6 Gene With The Susceptibility Of Type 2 Diabetes Mellitus

ObjectiveTo investigate the relationship between the polymorphism of LRP6 gene and type 2 diabetes mellitus(T2DM)susceptibility,and to evaluate the interaction effect of gene and environment factors on the occurance of T2 DM.MethodThe subjects were selected from the Rural Diabetes,Obesity and Lifestyle(Rural Diab)study.Cluster sampling method with natural village as a basic unit was used for this research.Subjects were recruited for a face-to-face questionnaire investigation and underwent the physical examination.Fasting blood samples were draw by professional physicians.Finally,a total of 1998 subjects aged 18-74 years were included in the statistics.Magnetic beads method was used for whole blood genomic DNA extraction and taqman fluorescence probe method was used to detect the genotypes of two locis.For continuous variables and categorical variables,the t test and chi-square test were performed to determine the distribution difference,respectively.Logistic regression models were set up to estimate the OR and 95% CI for the risk of T2 DM.Genetic risk score(GRS)model was set up to evaluated the combined effects of the two locis.The area under the receiver operating characteristic curve(ROC)and the net reclassification index(NRI)were used to evaluate the discrimination of T2 DM.The statistical analysis was performed using SAS 9.1software package(SAS Institute,USA).Haplo.stats package in R was applied to assess the haplotype of the two sites and their relation with T2 DM susceptibility.Multifactor dimensionality reduction(MDR)was used to assess the gene-environment interaction effect.ResultsThe study was included 1998 subjects,including 911 men and 1087 women,among which 349 were with T2 DM.1.The distribution of gender,age,culture,smoking status,alcohol intake,vegetables and fruits uptake and physical activity was statistically significant between the two groups(P<0.05).Compared to non T2 DM group,the values of waist circumstance,body mass index,systolic blood pressure,diastolic blood pressure,pulse pressure,pulse,total cholesterol,triglyceride,low density lipoprotein cholesterol and fasting plasma glucose were higher in the T2 DM group except the high density lipoprotein cholesterol level(P<0.05).2.The genotype and allele frequency distribution of rs11054731 and rs12823243 showed no statistically significant between the two groups(P>0.05).After adjusted for gender,age,smoking status,alcohol intake,high-fat intake,vegetables and fruits uptake,physical activity,family history of T2 DM and body mass index,for rs11054731,compared with AA genotype,individuals with AG genotype were at a higher risk of T2DM(OR=1.54,95%CI: 1.01-2.36).3.There were four haplotypes for rs11054731 and rs12823243.The frequency of haplotype GA,AT,AA,GT was no statistical difference between the two groups.Moreover,the four haplotypes were not associated with the risk of T2DM(P>0.05).The GRS of the two locis was not associated with the risk of T2 DM.4.After taking into the gentic information,the NRI were 3.06%,2.50%,0.79%respectively for the three models.However,the dicrimination of T2 DM was no statistically significant.There was no interaction effect between LRP6 gene and environment factors with the risk of T2DM(P>0.05).ConclusionIn current study,the AG genotype of rs11054731 was associated with the T2 DM susceptibility.The haplotype and GRS of the LRP6 gene were not associated with therisk of T2 DM.No interaction effect was found between the LRP6 polymorphism and environment factors.