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GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele

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Abstract

Myocardial infarction (MI) is a frequent outcome of coronary artery disease (CAD) and the key factor contributing to worldwide disability and death. Genetic factors contribute to the pathogenesis of CAD/MI, and SNP rs6903956 in the ADTRP gene was first found associated with CAD/MI in the Chinese Han population, which was successfully replicated in other cohorts. However, whether rs6903956 is a functional SNP and its risk mechanism to CAD/MI remains unknown. The ADTRP gene-encoded androgen-dependent TFPI regulating protein regulates vascular endothelial cell function, endothelial–monocyte adhesion, and thrombosis. The allele A of rs6903956, in particular, is associated with lower ADTRP mRNA levels in lymphocytes. In the current study, we found that SNP rs6903956 exhibits allelic differences in transcriptional activity by interacting with GATA2. Also, the A allele conferred a greater risk of CAD and MI, lowered transcriptional activity, and GATA2 binding ability as compared to the G allele. Our findings provide details on how rs6903956 regulates the expression of ADTRP and may provide novel insights into CAD pathology and susceptibility.

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Acknowledgments

We thank other members of The Institute of Infection and Inflammation.

Funding

This research was funded by the China National Natural Science Foundation (NSFC), Grants number 81900319, Natural Science Foundation grants of Hubei province, Grants number 2018CFB155, and Health Commission of Hubei Province Foundation, Grants number WJ2019H528.

Author information

Author notes

  1. Chunyan Luo, Bo Tang and Subo Qin authors made an equal contribution to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical College, China Three Gorges University, No.8, Da Xue Road, Yichang, 443002, Hubei Province, People’s Republic of China

    Chunyan Luo & Youqin Du

  2. The Institute of Infection and Inflammation, China Three Gorges University, Yichang, 443002, Hubei, China

    Chunyan Luo

  3. Department of Pharmacology, Institute of Material Medical, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Bo Tang

  4. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, 430074, China

    Subo Qin

  5. Department of Biochemistry, China Three Gorges University, Yichang, 443002, Hubei, China

    Chengfu Yuan

  6. Department of Cardiology, The People’s Hospital of China Three Gorges University, Yichang, 443000, Hubei Province, China

    Jian Yang

Authors
  1. Chunyan Luo
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  2. Bo Tang
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Contributions

Designed the work, CL and JY; carried out the experiments, CL, BT, SQ, CY, and YD; researching, analyzing, and interpreting the data, CL, BT, SQ, CY, YD, and JY; drafted the manuscript, CL and JY; visualization, CL and JY; supervision, CL and JY; funding acquisition, CL. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Chunyan Luo or Jian Yang.

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Luo, C., Tang, B., Qin, S. et al. GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele. Mol Genet Genomics 296, 799–808 (2021). https://doi.org/10.1007/s00438-021-01782-1

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  • DOI: https://doi.org/10.1007/s00438-021-01782-1

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