Association Of Bone Turnover Levels With MTHFR Gene Polymorphisms And Blood Lead Levels Among Pregnant Women In Wuhan, China

Objectives: Pregnancy is a critical stimulator of bone mineral resorption. We used to find that the MTHFR gene polymorphisms are related with BLLs among pregnant women. Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too. Therefore, the purpose of this study was to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women in Wuhan, China.Methods: The participants including pregnant and non-pregnant women were selected and recruited randomly during their routine prenatal or physical examination from July to October in 2012. A total of 1,000 participants, including 250 pregnant women in the first, second, and third trimesters and 250 non-pregnant women, were enrolled in the study. Finally, after excluding 27 participants unable to provide blood samples, 973 eligible participants(i.e., 234, 249, and 248 pregnant women in the first, second, and third trimesters, respectively, and 242 non-pregnant women) were included in the research. Automatic biochemical analyzer was used to determine plasma HCY levels, and specific ELISA kit was used to detect the concentration of plasma TRACP-5b and OC, respectively. The difference between measurements of bone turnover rate were explored by analysis of variance and non-parametric test(i.e., Kruskal Wallis H test and Mann-Whitney U test) under the group of genotype and various influencing factors. Multiple linear regression analysis was used to explore the factors on the changes of bone exchange rate and blood lead level.Results: The range of plasma HCY concentrations of all the subjects was from 0.031 to 35.84 ?mol/L. And the GM(GSD) of plasma HCY concentrations for the pregnant and non-pregnant women group were 2.27?mol/L(2.42) and 5.86?mol/L(1.89) respectively with significant difference(U= 30198.0, P<0.001). The minimum value of plasma OC concentrations was 0.89ng/ml, and the maximum value was 65.18ng/ml. The GM(GSD) of plasma OC levels was 7.67 ng/ml(1.81) and 14.1 ng/ml(1.91) for pregnant and non-pregnant women respectively. The mean has significant statistical difference(U=43192.0, P<0.001). Plasma TRACP-5b concentrations ranged from 0.61 U/L to 6.83 U/L for all subjects. The pregnant women and non-pregnant women had GM(GSD) of TRACP-5b level being 2.22(1.41) U/L and 1.72(1.32) U/L respectively. Compared with non-pregnant women, pregnant women had a significantly higher level of plasma TRACP-5b(U=48610.0, P<0.001). Results of multivariate linear regression analysis showed that the MTHFR gene 1298 CC homozygote carriers were more susceptible to yield higher plasma HCY levels than the 1298AA/AC carriers, with standardized coefficients of 0.086(P<0.05) and 0.104(P<0.01) for all the participants and the pregnant women, respectively. The MTHFR gene 1793 AA homozygote carriers were more likely to show higher plasma OC levels(standardized ? = 0.091, P < 0.01) than the 1793GG/GA carriers among all the subjects. Plasma HCY levels were positively correlated with BLLs among all the participants and the pregnant women as well, with standardized coefficients of 0.320(P<0.01) and 0.179(P<0.01), respectively. Plasma OC levels were positively associated with BLLs among the pregnant and non-pregnant women with standardized coefficients of 0.084(P<0.05) and 0.125(P<0.01), respectively.Conclusion: Plasma HCY and OC tend to decline during pregnancy and both decrease gradually with the increasing pregnancy trimester Plasma TRACP-5b present to increase during pregnancy, and the peak is in the middle trimester of pregnancy. MTHFR gene A1298 C polymorphisms are related with plasma HCY significantly, and G1793 A gene polymorphisms are associated with plasma OC significantly. Plasma HCY and OC levels are both related with blood lead level significantly. In conclusion, the bone turnover measurements(e.g., HCY and OC) in plasma are associated with the MTHFR gene A1298 C polymorphism and BLLs among Chinese pregnant women. The MTHFR gene A1298 C polymorphism-related HCY is a possible risk factor for increased BLLs among Chinese women.