Correlation Analysis Of The SNPs In The Folate Metabolic Pathway And Metabolic Capacity Of Homocysteine

Background:Periconceptional supplementation with the folic acid is the only determined intervention to prevent birth defects, such as congenital heart disease, cleft Lip and cleft Palate, and supplementation with the folic acid has been demonstrated to prevent50-70%of NTD cases.Folic acid plays an important role in the synthesis of DNA and RNA as an enzyme cofactor by participating in homocysteine metabolism. Therefore, homocysteine concentration is considered to be important physiological indices of metabolic pathway of folic acid in vivo, and researchers have found that folic acid and homocysteine concentration have a close relationship with a variety of birth defects. Researchers have found that SNPs in genes that code for enzymes involved in folate metabolism and the closely-related homocysteine has produced an effect on the metabolism of folate and homocysteine. Especially the MTHFR C677T single-nucleotide polymorphism (SNP) has been associated with a modest increased risk of NTDs. However, the function of only one SNP on the birth defects is very small. Whether a series of gene polymorphism could have a greater impact has not been elucidated. Therefore, the research of the impact of the SNPs in genes that code for enzymes involved in folate metabolism on the metabolism of homocysteine, is one of the current problems to be solved urgently.Methods:Using cross-sectional data, we investigated18single nucleotide polymorphisms(SNPs) in9genes in the complex folate pathway, and detected the serum folate and homocysteine of386cases of Chinese Han nationality in Shanghai, to explore the impact of the SNPs on the metabolism of folate and homocysteine. Finally, we used support vector machines to predict best model of homocysteine and folic acid metabolism.Result:The association analysis showed that only the genotypic frequency distributions of loci (rs1801133and rs3737965) on MTHFR were statistically significant with the value of serum of folic acid and Hey. When we did the two joint analysis with rs1801133, we found rs1051266, rs3737890; rs2851391and rs234713were statistically significant with the value of serum of folic acid and Hey. In the SVM regression, we got a model to predicate the folate and plasma homocysteine concentrations:rs3733890AG, rs234713AG, the rs3737965CT had a protective effect on metabolism of folate and Hey, the rs1801131CA, rs1801133TT had damaging effect on the metabolism of folate and Hey. We apply these models to score the SNPs, finding when the score is more than0.2points, Hey concentration significantly increased.Conclusions:The combination of SNPs in genes that code for enzymes involved in folate metabolism and homocysteine are in close relationship of the concentration of homocysteine. SVMs for association studies of SNPs in candidate genes shows considerable promise in predict the metabolism of folate and homocysteine. Our research provided an important clue for individualized dose of periconceptional supplementation with folic acid, which will be helpful to clarify the genetic mechanism of metabolism of folic acid and homocysteine.