title: Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac septal defects in a Han Chinese population.
abstract: BACKGROUND
  Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population.
  
  
  METHODS
  Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression.
  
  
  RESULTS
  We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either.
  
  
  CONCLUSIONS
  Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population.
authors.affiliation: The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jian-Yuan
authors.initials: JY
authors.lastname: Zhao
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Sun
authors.forename: Zhuo-Ya
authors.initials: ZY
authors.lastname: Gu
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Er-Li
authors.initials: EL
authors.lastname: Wang
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Duan
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D016022:Case-Control Studies; D002384:Catalysis; D002648:Child; D002675:Child, Preschool; D002681:China; D004247:DNA / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006343:Heart Septal Defects / Q000208:ethnology* / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D011687:Purines; D011743:Pyrimidines; D006710:Homocysteine; D004247:DNA; D013940:Thymidylate Synthase