Association Of Polymorphism In The CDKN2A/2B Gene With Gestational Diabetes Mellitus

Objective: Cyclin dependent kinase inhibitor2A/2B (CDKN2A/2B) can inhibit CDK4, a powerful regulator of pancreatic beta cell replication, then induce islet dysplasia and diabetes. The research object is the gestational diabetes mellitus (GDM) patients, female type2diabetes and normal pregnant women living in the southwest of Shandong Province. This study is to investigate the genotype’s frequency and the allele distribution of single nucleotide polymorphism of rs10811661in CDKN2A/2B, and study its correlation with metabolic indices. We also study the association of gene polymorphism with gestational diabetes, and explore its mechanism.Methods: The study objects were divided into three groups: the normal glucose tolerance group (NGT), the gestational diabetes group(GDM), type2diabetes group (T2DM). The GDM group were chosed from the women during24to28weeks of pregnancy after75g OGTT. GDM was diagnosed according to the criteria of American diabetes association(ADA) criteria of2010. The normal glucose tolerance women were selected into NGT group. The patients of T2DM group were selected from the inpatients in Jining Medical College affiliated hospital at the same time. The120normal glucose tolerance pregnant women,150gestational diabetes patients and120type2diabetes patients were recruited. Venous blood were collected for measuring biochemical indicators and extracting DNA. We determined the genotypes of rs10811661in CDKN2A/2B by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Some samples were sequenced to check the genotype. Using SPSS13.0software to analyse the datas. There is significant difference when P value was below0.05.Results:(1) Each of the three groups had TT, TC and CC genotype. In NGT group, the frequency of TT, TC and CC genotype were21.5%、43.3%、29.2%. In GDM group, the frequency of TT, TC and CC genotype were38.7%、44.0%、17.3%. In T2DM group, the frequency of TT, TC and CC genotype were37.5%、49.2%、13.3%. NGT�'GDM�'T2DM, the frequency of risk allele T was49.2%、60.7%,62.1%respectively.There was statistic value about the genotype frequency distribution between GDM and NGT, T2DM and NGT (P<0.05). The frequence of risk allele T in GDM group and T2DM group was significant higher than in NGT group(P<0.05). But the frequency difference of genotype and risk allele between GDM and T2DM did not have statistic value(P>0.05).(2)NGT�'GDM�'T2DM, HOMA-IR increased and HOMA-β decreased gradually. The difference of HOMA-β had statistic value between the NGT group and the GDM group in the TT, TC and CC genotype (P<0.05).(3) Applying logistic regression analysis of GDM and NGT, the genotype TT with GDM had increased risk (P=0.018, OR=2.315). Triglyceride was associated with GDM(P=0.044, OR=2.244).Conclusions:(1) The polymorphisms of rs10811661in CDKN2A/2B existed in the women of southwest of Shandong Province.(2) The allele T of rs10811661in CDKN2A/2B was one of the risk alleles of GDM, CDKN2A/2B might be one of the GDM susceptible genes.(3) CDKN2A/2B might be one of the both GDM and T2DM susceptible genes...