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

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Abstract

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.

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Funding

This study was funded by special fund for basic scientific research projects of Henan Provincial Institute (Grant Number 2014JBKY005), Henan Science Department.

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Authors and Affiliations

  1. Henan Research Institute of Population and Family Planning, National Health and Family Planning Commission Key Laboratory of Birth Defects Prevention, No. 26, Jingwu Road, Jinshui, Zhengzhou, 450002, China

    Fengyu Wang, Haili Wang, Lina Wang, Shiyuan Zhou, Mingxiu Chang, Jiping Zhou, Yongheng Dou, Yanli Wang & Xiangdong Shi

Authors
  1. Fengyu Wang
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  2. Haili Wang
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  3. Lina Wang
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  4. Shiyuan Zhou
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  6. Jiping Zhou
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  7. Yongheng Dou
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  8. Yanli Wang
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  9. Xiangdong Shi
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Correspondence to Shiyuan Zhou.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from their parents of all individual participants included in the study.

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Wang, F., Wang, H., Wang, L. et al. Association Between Single Nucleotide Polymorphisms in NFATC1 Signaling Pathway Genes and Susceptibility to Congenital Heart Disease in the Chinese Population. Pediatr Cardiol 37, 1548–1561 (2016). https://doi.org/10.1007/s00246-016-1469-5

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  • DOI: https://doi.org/10.1007/s00246-016-1469-5

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