title: The effect of multiple single nucleotide polymorphisms in the folic acid pathway genes on homocysteine metabolism.
abstract: OBJECTIVE
  To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism.
  
  
  METHODS
  Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level.
  
  
  RESULTS
  SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid.
  
  
  CONCLUSIONS
  SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid.
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China ; Department of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
authors: Shuang
authors: S
authors: Liang
authors: State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai 200433, China.
authors: Yuanpeng
authors: Y
authors: Zhou
authors: Children's Hospital of Fudan University, Shanghai 201102, China.
authors: Huijun
authors: H
authors: Wang
authors: Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Yanyan
authors: Y
authors: Qian
authors: Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Duan
authors: D
authors: Ma
authors: State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai 200433, China.
authors: Weidong
authors: W
authors: Tian
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors: Vishwani
authors: V
authors: Persaud-Sharma
authors: Central Lab, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
authors: Chen
authors: C
authors: Yu
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China ; Department of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
authors: Yunyun
authors: Y
authors: Ren
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors: Shufeng
authors: S
authors: Zhou
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China ; Department of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China ; Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Xiaotian
authors: X
authors: Li
mesh_terms: D000328:Adult; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000235:genetics*; D006710:Homocysteine / Q000097:blood / Q000235:genetics*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy
chemical_list: D006710:Homocysteine; D005492:Folic Acid