Relationship Between CDKAL1 And CDKN2A/2B Genes With Type 2 Diabetes In Chinese Han Individuals

Objective:CDK5 has a role in the loss of beta cell function under glucotoxic conditions.CDKAL1 gene can inhibit the activation of CDK5.CDK4 modulates the generation of pancreatic beta cell effectively.The product of CDKN2A/2B can inhibit CDK4.The excessive express of CDKN2A/2B will result in the decrease of beta cell generation.The polymorphism of above-mentioned genes is closely associated with impaired beta cell function,the decrease of insulin secretion and the development of type 2 diabetes.In the study,randomly selected,unrelated patients with type 2 diabetes,patients with impaired glucose regulation and normal controls which glucose tolerance was normal were included.We genotyped the genes to explore the relation between the two genes variation and type 2diabetes.Methods:We screened the patients with type 2 diabetes,patients with impaired glucose regulation and normal controls with OGTT.After an overnight fasting,all subjects' venous blood was drawn for DNA extraction and for measuring some biochemistry parameters.Using PCR-RFLP we detected the rs7754840 G/C and rs10811661T/C polymorphism in all subjects.We sequenced the genes.We analysized the clinical datas using the SPSS13.5 software.Results:(1)HOMA-IR increased and ISI decreased gradually in the three groups, the difference had statistic value(P＜0.05),but there was no significant difference in the three kind of genotype derived from the same group.(2)In this study,we found that rs7754840 had three kind of genotypes in the three groups.The frequence of risk allele C/C homozygote and risk allele C in type 2 diabetes group was significant higher than in normal control group(P＜0.05).That the carrier of C is stricken by diabetes is 1.48 folds of carrier of G.(3)we found that rs10811661 had three kind of genotypes.The frequence of risk allele T/T homozygote is 37.5%,and the frequence of risk allele T is 59.5%in type 2 diabetes group,which is significant higher than in normal control group(P＜0.05).That the carrier of T is stricken by diabetes is 1.38 folds of carrier of C.Conclusion:(1)CDKAL1 and CDKN2A/2B genes variants existed in Tianjin population.(2)The polymorphism of above-mentioned genes is closely associated with impaired beta cell function,the decrease of insulin secretion,which is not associated with insulin resistance and insulin sensitivity.We confirmed that CDKAL1 and CDKN2A/2B genes were the diabetes susceptibility genes.(3)CDKAL1 and CDKN2A/2B variations,age and TG were the risk factors for diabetes,while HOMA-βwas the protective factor.