title: A genetic variant in vitamin B12 metabolic genes that reduces the risk of congenital heart disease in Han Chinese populations.
abstract: BACKGROUND
  Genome-wide association studies on components of the one-carbon metabolic pathway revealed that human vitamin B12 levels could be significantly influenced by variations in the fucosyltransferase 2 (FUT2), cubilin (CUBN), and transcobalamin-I (TCN1) genes. An altered vitamin B12 level is an important factor that disturbs the homeostasis of the folate metabolism pathway, which in turn can potentially lead to the development of congenital heart disease (CHD). Therefore, we investigated the association between the variants of vitamin B12-related genes and CHD in Han Chinese populations.
  
  
  RESULTS
  Six variants of the vitamin B12-related genes were selected for analysis in two independent case-control studies, with a total of 868 CHD patients and 931 controls. The variant rs11254363 of the CUBN gene was associated with a decreased risk of developing CHD in both the separate and combined case-control studies. Combined samples from the two cohorts had a significant decrease in CHD risk for the G allele (OR = 0.48, P = 1.7×10⁻⁵) and AG+GG genotypes (OR = 0.49, P = 4×10⁻⁵), compared with the wild-type A allele and AA genotype, respectively.
  
  
  CONCLUSIONS
  Considering the G allele of variant rs11254363 of the CUBN gene was associated with an increased level of circulating vitamin B12. This result suggested that the carriers of the G allele would benefit from the protection offered by the high vitamin B12 concentration during critical heart development stages. This finding shed light on the unexpected role of CUBN in CHD development and highlighted the interplay of diet, genetics, and human birth defects.
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: Jue
authors.initials: J
authors.lastname: Wang
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.affiliation: Children's Hospital Shanghai, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Peng
authors.affiliation: Children's Hospital Shanghai, Fudan University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hou
authors.affiliation: Children's Hospital Shanghai, Fudan University, Shanghai, China.
authors.forename: Shu-Na
authors.initials: SN
authors.lastname: Sun
authors.affiliation: Children's Hospital Shanghai, Fudan University, Shanghai, China.
authors.forename: Yong-Hao
authors.initials: YH
authors.lastname: Gui
authors.affiliation: Institute of Cardiovascular Disease General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Duan
authors.affiliation: Institute of Cardiovascular Disease General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.affiliation: The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China ; Children's Hospital Shanghai, Fudan University, Shanghai, China ; The Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D005819:Genetic Markers; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006333:Heart Failure / Q000151:congenital* / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk; D014155:Transcobalamins / Q000235:genetics; D014805:Vitamin B 12 / Q000378:metabolism*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D005819:Genetic Markers; D011956:Receptors, Cell Surface; D014155:Transcobalamins; D014805:Vitamin B 12; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C029486:intrinsic factor-cobalamin receptor