Slc30a8 Gene, Cdkal1 Gene And Gestational Diabetes Research

ObjectiveTo find the best cut-point of 50g glucose challenge test to predict gestational diabetes mellitus(GDM) and to study the single nucleotide polymorphism of rs13266634 and rs2466293(the genotype and the frequency) in SLC30A8 gene and of rs10946398,rs9465871,rs7756992 and 7754840 in CDKAL1 gene and its association with GDM.The predictive value of genetic testing for prediction of gestational diabetes mellitus in gestatioinal women is unclear.Methods 1861 Chinese pregnant women were included in our study.Of which 300 women with a plasma glucose value≤7.8mmol/L 1h after a standard 50-g GCT(GCT negative).1561 women had a plasma glucose value≥7.8mmol/L 1h after 59-g GCT underwent 100-g OGTT.Diagnosis of GDM was based on ADA criteria.There were 651 case of NGT,301 case ofIGT,609 case of GDM.The ROC analysis of was done by OGTT.ISI-Matsuda and insulin sensitivity-secretion index(ISSI) were analyzed.The polymorphism of SLC30A8 gene and CDKAL1 gene was genotyped by ligase detection reaction.The predictive value of these polymorphisms was examined using logistic regression analysis.The discriminative accuracy of the prediction models was assessed by the area under the receiver operating characteristic curves(AUCs).Result:1,Mean ISSI was highest in the NGT group,followed by that in the IGT group and then GDM group(overall p＜0.001).2,The areas under the ROC curve were 0.779 for GDM.The cut-point of GCT with the best equilibrium between sensitivity and specificity was 7.8mmol/l for GDM.3,In GDM+IGT group,the frequency of C allele and CC genotype of rs13266634 were significantly higher than those in the NGT group(P＜0.05);the TT genotype was significantly lower than that of the NC group(P＜0.05).The C-allele of rs13266634 significantly increased GDM risk with an allelic odd ratio(OR) of 1.29. Compared with non-carriers,homozygous carriers of C allele were liable to have GDM with OR=1.47.Mean ISSI was highest in the TT genotype,followed by that in the CT genotype and then CC genotype(overall p=0.002) in the GDM+IGT group, NGT group was the same.4,In GDM+IGT group,the frequency of C allele and CC genotype of rs10946398 were significantly higher than those in the NGT group(P＜0.05);the TT genotype was significantly lower than that of the NC group(P＜0.05).The C-allele of rs10946398 significantly increased GDM risk with an allelic odd ratio(OR) of 1.25. Compared with non-carriers,homozygous carriers of C allele were liable to have GDM with OR=1.49.Mean ISSI was highest in the AA genotype,followed by that in the CA genotype and then CC genotype in the GDM+IGT group,(overall P=0.009).5,The AUC wsa 0.553(95%CI:0.520-0.586) for predicton based on the genetic polymorphisms;0.620(95%CI:0.588-0.652) for age and BMI.Conclusion1,The cut-point of GCT with the best equilibrium between sensitivity and specificity was 7.8mmol/l for GDM.2,These result indicate that C allele polymorphism of rs13266634 site in SLC30A8 gene and C allele polymorphism of rs13266634 site inCDKAL1 might be susceptible genes of GDM in the Chinese Han pregnant women.3,Combined genetic variants has low predictive value fou gestational diabetes mellitus.