Association Of Single Nucleotide Polymorphisms Of CDKAL1 And KCNQ1 Genes With Gestational Diabetes Mellitus

Objective: We aim to explore the relationships between single nucleotide polymorphisms(SNPs)of pancreatic beta cell function related genes(CDKAL1 and KCNQ1 gene)and genetic susceptibility to gestational diabetes mellitus(GDM)in the population of Guangxi,which will contribute to elucidating molecular mechanisms behind the development of GDM and providing scientific basis for treatment and prevention of GDM.Methods: A hospital-based case-control study was conducted in 553 GDM patients and 721 healthy controls.We screened 6 candidate SNPs by online software and tools like SNPinfo(CDKAL1: rs7756992,rs7754840,rs9465994;KCNQ1: rs231362,rs163182,rs2283194),which were finally detected by Sequenom MassARRAY genotyping technique.We analysed the distributions of genotypes between the cases and the controls and analysed whether genotype distributions in controls were in Hardy-Weinberg equilibrium.Multivariate Logistic regression was used to calculate the 95% confidence interval(CIs)and odds ratios(ORs)for analyzing the relationship between candidate SNPs and genetic susceptibility to GDM.Results: The results of our study indicated that the age,body mass index(BMI),systolic blood pressure,diastolic blood pressure,fasting blood glucose(FPG),1 hour postprandial blood glucose of OGTT(OGTT 1h),2 hour postprandial blood glucose of OGTT(OGTT 2h),Hemoglobin A1c(HbA1c),total cholesterol(TC)and low density lipoprotein cholesterol(LDL)levels were significantly higher in cases.The genotype frequency distributions in controls were consistent with Hardy-Weinberg equilibrium.The results of our study showed that two SNPs(rs9465994 and rs7754840)located in CDKAL1 gene were significantly related to the risk of GDM.After correction for age and body mass index(BMI),the AG genotype of rs9465994 in CDKAL1 gene was found to be associated with decreased risk of GDM(OR=0.71,95%CI=0.51~ 0.99,P=0.049).However,the GC genotype of rs7754840 in CDKAL1 gene contributed to increased risk with GDM when compared with the GG genotype(OR=1.41,95%=1.09~1.84,P=0.010),meanwhile,the result was significant under the dominant model(OR=1.41,95%=1.10~1.81,P=0.007).Conclusions: The CDKAL1 gene rs7754840 polymorphism and rs9465994 polymorphism were found to be associated with GDM in the population of Guangxi.The mutant,C allele of the rs7754840 SNP might be a risk variant and the mutant,AG genotype of the rs9465994 SNP might be a suggestive protective variant against GDM development.Our results need to be further verified by the studies of larger sample size or different ethnic groups,of which the mechanism should be elucidated by the functional cytobiology experiment.