Journal of Genetics

, 98:45 | Cite as

Minor alleles of genetic variants in second heart field increase the risk of hypoplastic right heart syndrome

  • Enshi Wang
  • Yu Nie
  • Xuesong Fan
  • Zhe Zheng
  • Haiyong Gu
  • Hao Zhang
  • Shengshou HuEmail author
Research Article


Hypoplastic right heart syndrome (HRHS) is characterized by hypoplastic right ventricle (RV); Numerous transcriptional cascades in the second heart field (SHF) regulate RV development. The relationship of SHF gene variants with human HRHS remains unknown. The whole lengths of 17 SHF genes were sequenced in 16 HRHS, and the selected single-nucleotide variants (SNVs) were then genotyped in HRHS, other congenital heart disease (CHD) and healthy control. Luciferase assay was performed to verify the effect of FOXC2: rs34221221 \(\hbox {A}{>}\hbox {G}\) and TBX20: rs59854940 \(\hbox {C}{>}\hbox {G}\) at the transcription level. There were 151 (12.86%) novel SNVs after sequence analysis, of which three were in exons (one was synonymous SNV and two were nonsynonymous SNVs), two in promoter, and most SNVs (89.95%) were in intronic regions. Genotype analyses revealed that the minor alleles of FOXC2: rs34221221 \(\hbox {A}{>}\hbox {G}\) and TBX20: rs59854940 \(\hbox {C}{>}\hbox {G}\) could increase HRHS risk (\(P{<}0.05\)), but not in other CHD or healthy control. Luciferase assay showed that the minor G allele in rs34221221 significantly increased FOXC2 transcription while in rs59854940 it decreased TBX20 transcription significantly. Novel variants of SHF gene associated with HRHS were identified. Minor alleles in two variants from FOXC2 and TBX20 could increase the risk of HRHS.


hypoplastic right heart syndrome single-nucleotide variant second heart field transcription factor congenital heart disease 



This study was supported by the National Natural Science Foundation of China (grant no. 81400242, 81430006 and 81441010) and the National Basic Research Development Program in China (Program 973: 2010CB529505).

Supplementary material

12041_2019_1092_MOESM1_ESM.docx (191 kb)
Supplementary material 1 (docx 191 KB)


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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Enshi Wang
    • 1
    • 2
  • Yu Nie
    • 2
  • Xuesong Fan
    • 3
  • Zhe Zheng
    • 1
  • Haiyong Gu
    • 1
  • Hao Zhang
    • 1
    • 2
  • Shengshou Hu
    • 1
    • 2
    Email author
  1. 1.Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingPeople’s Republic of China
  3. 3.Department of Clinical Laboratory Center, Beijing An Zhen Hospital, Capital Medical UniversityBeijing Institute of Heart, Lung and Blood Vessel DiseasesBeijingPeople’s Republic of China

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