title: Characterization of nodal/TGF-lefty signaling pathway gene variants for possible roles in congenital heart diseases.
abstract: BACKGROUND
  Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD).
  
  
  METHODS
  We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software.
  
  
  RESULTS
  Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
  
  
  CONCLUSIONS
  The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Deng
authors.affiliation: Intensive Care Unit, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Fei-Feng
authors.initials: FF
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Er-Ying
authors.initials: EY
authors.lastname: Zhao
authors.affiliation: Department of Oncology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hao
authors.affiliation: Intensive Care Unit, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Kai-Jiang
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China; Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001483:Base Sequence; D002648:Child; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D055458:Left-Right Determination Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D055457:Nodal Protein / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics; D015291:Transforming Growth Factors / Q000378:metabolism*
chemical_list: D055458:Left-Right Determination Factors; D055457:Nodal Protein; D022821:RNA Splice Sites; D015291:Transforming Growth Factors
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