Association Study Of IGF2BP2,CDKN2A/B, KCNJ11 Genetic Polymorphisms With Type 2 Diabetes In Chinese Population

Objective:Type 2 diabetes mellitus is a group of chronic and complex disease characterized as increased blood plasma glucose, it is the result of combined action of genetic and environmental factors, and genetic factor plays an important role in the process of its onset. As genome-wide association studies (GWAS) is widely used, many SNPs which associated with type 2 diabetes susceptibility are screened out. In European, it has been found that several genes associated with type 2 diabetes susceptibility. IGF2BP2, CDKN2A/B and KCNJ11 gene were proved strong correlation with type 2 diabetes susceptibility, but there were different genotypes distribution in different regions and ethnic groups. This study aims to investigate the association of IGF2BP2, CDKN2A/B and KCNJ11 genetic polymorphisms with the susceptibility of type 2 diabetes in Chinese population.Methods:Rs4402960 of IGF2BP2 gene, rs10811661 of CDKN2A/B gene and rs5215 of KCNJ11 gene in a case-control study from a Chinese population, including 323 type 2 diabetes patients,57 impaired fasting glucose (IFG) and 307 healthy controls. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method combined with gene sequencing method was employed to genotypes. A Chi-square test was used to calculate the difference of genotype and allele frequencies for each SNP between the case and control group. Odds ratios (ORs) with 95 percent confidence intervals (CIs) were assessed for the risk allele of each SNP by unconditional logistic regression with adjustment for gender and age. The difference of clinical indexes between case and the control group was analysed by Independent-Samples t test, and the associations of different genotypes and clinical indexes were examined by one-way ANOVA, respectively. MDR was used to analyse the interaction among genes.Results:The results showed that rs4402960 of IGF2BP2 gene and rs10811661 of CDKN2A/B gene are associated with the susceptibility of type 2 diabetes in Chinese population (P< 0.05), while rs5215 of KCNJ11 gene was found no correlation (P> 0.05). MDR analysis results indicated that the functions of three loci were independent. Further the analysis results of cumulative effect of rs4402960 and rs10811661 showed that a significantly higher proportion of participants with type 2 diabetes carry increasing numbers of risk alleles, compared with participants with health, and the risk of type 2 diabetes and fasting plasma glucose would increase with the increase of carrying the risk allele. Analysing the relationship of three genes with impaired fasting glucose (IFG) showed no correlation among them.Conclusion:Our results suggest that the polymorphisms of IGF2BP2 gene and CDKN2A/B gene associated with the susceptibility of type 2 diabetes in Chinese population, but the association of KCNJ11 gene polymorphism and type 2 diabetes is not found in Chinese population.