Association Between Single Nucleotide Polymorphisms in NFATC1 Signaling Pathway Genes and Susceptibility to Congenital Heart Disease in the Chinese Population.

The nuclear factor of activated T lymphocytes (NFATC1) signaling has been demonstrated to play important roles in cardiac valve and septal development. Genetic variants in genes involved in NFATC1 signaling may affect their expression and promote the formation of congenital heart disease (CHD). The goal of this study was to investigate the associations of single nucleotide polymorphism (SNP) in seven genes (NFATC1, VEGFR, VEGF, RANKL, FGFR1, BCL-6 and ZNRD1) with the risk of CHD. Twenty-nine polymorphisms were genotyped by using MassARRAY RS1000 platform in 277 CHD child patients and 293 controls from the Henan Province in China. Fours SNPs were excluded for the association analysis because of deviation from the Hardy-Weinberg equilibrium. Of the 25 SNPs, only two were found to be significantly associated with increased CHD risk after Bonferroni correction (RANKL, rs4531631: homozygous, AA vs. GG; OR 2.38, 95 % CI 1.40-4.07, p = 0.001; recessive, AA vs. AG + GG; OR 2.54, 95 % CI 1.53-4.22, p = 0.0003; FGFR1, rs13317: recessive, CC vs. CT + TT; OR 2.06, 95 % CI 1.30-3.25, p = 0.00196). Our findings suggest rs4531631 and rs13317 may be potential biomarkers for genetic diagnosis and treatment of CHD.

A novel FBN2 mutation cosegregates with congenital contractural arachnodactyly in a five-generation Chinese family.

We identified a novel heterozygous mutation (c.4177T>G and p.Cys1393Gly) in FBN2 that cosegregated with congenital contractural arachnodactyly (CCA) in a five-generation Chinese family. This mutation may cause the loss of the disulfide bond between Cys 1393 and Cys 1378 residues of fibrillin-2. Our study expands the genetic profile of CCA.