The Impact Of VDR Gene Polymorphism On Association Of Vitamin D With Gestational Diabetes Mellitus

ObjectiveTo describe the change trend of vitamin D status in Hefei during pregnancy from 2015 to 2018 by the prospective birth cohort.To estimate the association of 25(OH)D levels and vitamin D supplementation in pregnant women with the risk of gestational diabetes mellitus(GDM),and to determine the threshold of 25(OH)D concentration in pregnant women that significantly affects the association of 25(OH)D with GDM and glucose metabolism indexes.Furthermore,the association between vitamin D receptor(VDR)gene polymorphism and the risk of GDM was further analyzed.And,the impacts of vitamin D supplementation on the prevention of GDM in pregnant women with different genotypes were estimated.MethodsFrom March 2015 to February 2019,5 594 pregnant women were recruited from three hospitals in hefei.We collected information about sociodemographic characteristics,health status,lifestyle and dietary habits of pregnant women by questionnaire.We ecorded vitamin D supplementation in early pregnancy(including frequency and daily dose).Venous blood was collected on the day pregnant women were recruited.After that,the blood samples were centrifuged,the upper serum was taken for 25(OH)D level,and the DNA was extracted from the lower blood cells for VDR gene polymorphism.All pregnant women underwent 75 g oral glucose tolerance test at 24 to 28 weeks of pregnancy to obtain the indexes of fasting plasma glucose,1-h plasma glucose and 2-h plasma glucose.The index of area under the curve of glucose was calculated using the approximate trapezoid method,and GDM was diagnosed at the same time.ResultsIn this study,the average serum 25(OH)D levels in pregnant women was(39.38±16.29)nmol/L,and the rate of vitamin D deficiency was 77.4%(4 331/5 594).A total of 1 032(18.4%)pregnant women were diagnosed with GDM.From 2015 to 2018,the vitamin D levels of pregnant women in hefei showed a downward trend(P < 0.001),and the rate of vitamin D deficiency showed an upward trend(P < 0.001).After adjusting for general demographic characteristics,health status,lifestyle and dietary habits during pregnancy,compared with women with severe vitamin D deficiency(25(OH)D < 25 nmol/L),women with 25(OH)D levels above 50 nmol/L had a significantly lower risk of GDM(50-75 nmol/L: RR = 0.72,95%CI: 0.57,0.91;≥75 nmol/L: RR = 0.38,95%CI: 0.22,0.65).Restricted cubic spline hazardmodel were used to analyze the association between vitamin D and the risk of GDM.After adjusting for related confounding factors,the results showed that when the 25(OH)D levels was lower than 50 nmol/L,there was no statistical correlation between the 25(OH)D levels and the risk of GDM,while when the level of 25(OH)D was higher than 50 nmol/L,25(OH)D was significantly correlated with the risk of GDM.Polynomial curve fitting model and piecewise linear regression model were used to analyze the correlation between the level of 25(OH)D and glucose metabolism indexes(FPG,PG-1h,PG-2h and AUC).The results showed that only when the level of 25(OH)D was higher than 50 nmol/L,with the increase of the 25(OH)D levels,the concentrations of FPG,PG-1h and AUC significantly decreased.Compared with pregnant women who did not take vitamin D,only those who received daily vitamin D supplementation had a significantly lower risk of GDM(RR = 0.84,95%CI: 0.71,0.98),with a level of 25(OH)D close to 50 nmol/l(48.89 nmol/l).Gene polymorphisms at Bsm I(rs1544410)and Taq I(rs731236)sites in VDR genes are associated with the risk of GDM.After adjusting for related confounders,CT genotypes had lower 25(OH)D levels and higher risk of GDM than CC genotypes in Bsm I(RR = 1.91,95%CI :1.35,2.69).Compared with AA genotypes in Taq I,GA genotypes had lower 25(OH)D levels and higher risk of GDM(RR = 2.02,95%CI :1.46,2.80).Compared with women who did not receive vitamin D,women who received vitamin D daily had higher 25(OH)D levels and a lower risk of GDM(RR = 0.73,95%CI :0.54,0.97)in CC genotype at Bsm I.There were similar results for women with AA genotype at Taq I.The 25(OH)D levels increased with the frequency of vitamin D supplementation(P < 0.001),but the risk of GDM did not change significantly in CC genotype at Bsm I.There were similar results for women with GA genotype at Taq I.Further analysis showed that the risk of GDM in CT genotype at Bsm I was significantly higher than that in CC genotype(RR = 2.41,95%CI :1.38,4.19),and risk of GDM in GA genotype at Taq I was significantly higher than that in AA genotype(RR = 2.09,95%CI :1.20,3.62)for women who regularly take vitamin D.ConclusionsThe vitamin D deficiency in pregnant women was serious and the vitamin D levels continued to decline.There is a non-linear association of the 25(OH)D levels with the risk of GDM and glucose metabolism indexes.50 nmol/L may be the threshold level of 25(OH)D that impact the association of 25(OH)D with the risk of GDM.The risk of GDM was significantly reduced only in pregnant women with 25(OH)D levels above 50 nmol/L.Pregnant women who received 400 to 600 IU of vitamin D daily had a 25(OH)D level of up to 50 nmol/L,significantly reducing the risk of GDM.The Bsm I site Taq I site in the VDR gene is associated with GDM and may influence the risk of GDM by affecting the 25(OH)D levels.In the future,more high-quality randomized controlled trials are needed to clarify the potential protective impact of vitamin D supplementation on GDM.