Association Of Single Nucleotide Polymorphisms Of CDKN2A/B Genes With Gestational Diabetes Mellitus

Objective: To investigate the association between cyclin-dependent protein kinase inhibitor 2A/B(CDKN2A/B)gene single nucleotide polymorphisms(SNPs)and the risk of genetic susceptibility to gestational diabetes mellitus(GDM)in population,so as to provide experimental gist for further study on the pathogenesis of GDM.Methods: This study based on the hospital cases-control method,from between September 2014 and June 2016,all pregnant women were screened in Affiliated Hospital Guilin Medical University and Guilin women and children Hospital.459 with GDM group and 571 pregnant women who had the regular antenatal examination with contral group women were included in the study.We screened 7 candidate SNPs of CDKN2A/B gene,including rs2811710(T>C)、rs3088440(G>A)and rs7036656(T>C)of CDKN2 A gene,CDKN2 B rs1063192(T>C)、 rs3217986(A>G)and rs3217992(G>A)of CDKN2 B gene andCDKN2A/B gene rs10811661(C>T),were genotyped by using Sequenom MassARRAY genotyping system platform.The multi-factor logistic regression analysis was adopted with OR and it’s corresponding 95% CI analyze the association between the candidate SNPs and the risk of GDM,and adjusted for age,BMI,systolic blood pressure and diastolic blood pressure.Multifactorial dimensionality reduction(MDR)was used to analysis the interaction in SNPs which was statistically association with the risk of GDM.Results:1.According to general clinical data analysis results,the age、 BMI、fasting plasma glucose、1h-PG、2h-PG、HbA1c、systolic blood pressure and diastolic blood pressure were significantly higher in the GDM group compared with those in the controls(P<0.05).2.According to the Chi-square fitting test,the genotype frequency distributions in CDKN2 A gene rs3088440(G>A)and rs7036656(T>C),CDKN2 B gene rs1063192(T>C)and rs3217986(A>C)and CDKN2A/B gene rs10811661(C>T)were consistent with Hardy-Weinberg equilibrium in the control group.3.The Logistic regression analysis showed that,CDKN2A/B gene rs10811661 was statistically associated with the risk of GDM.Comparing with CC genotype,TC/TT genotypes was significantly increased the risk of GDM(OR=1.44,95%CI=1.04~1.20,P=0.029).No othe SNPs were to be associated with the risk of GDM in this study(P>0.05).Stratification analyses indicated that,TC/TT genotypes in rs10811661 was strongly associated with an increased risk of GDM among pregnant women older than 29(OR=1.65,95%CI= 1.09~2.51,P=0.018).After adjusting for age、BMI、systolic blood pressure and diastolic blood pressure(OR=1.61,95%=1.04~2.50,P=0.034),the difference was statistically significant.In pregnant women with a normal BMI(<24),those who carried TC/TT genotypes compared with CC genotypes was associated with an increased risk of GDM group(OR=1.52,95%CI=1.03~2.26,P=0.036).4.Multifactor dimensionality reduction(MDR)analysis showed that the SNPSNP interaction had a combined cumulative effect and was statistically associated with an increased risk of GDM,rs10811661 was the optimal unit point model(CV Consistency=7/10,Testing balance accuracy=0.500,P=0.028),and rs10811661-rs7036656-rs1063192-rs3217986 was optimal combined action medel(CV Consistency=10/10,Testing balance accuracy=0.0485,P<0.001).Conclusions: The CDKN2A/B gene rs10811661 polymorphisms are associated with the risk of GDM,and single or combineding effects of SNPs maybe affect the susceptibility of pregnant women to GDM.Our findings need further evaluation in a various regions and races setting,and related mechanisms explored through cellular and molecular experiments.