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CCN1 gene polymorphisms associated with congenital heart disease susceptibility in Northwest Chinese population from different high-altitude areas

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Abstract

High-altitude hypoxic environment exposure is considered one of the risk factors for congenital heart disease (CHD), but the genetic factors involved are still unclear. CCN1, one of the synergistic molecules in the hypoxic response, is also an indispensable molecule in cardiac development. Considering that CCN1 may play an important role in the occurrence of CHD in high-altitude areas, we investigated the association between CCN1 polymorphisms and CHD susceptibility in Northwest Chinese population from different high-altitude areas. We conducted a case-control study with a total of 395 CHD cases and 486 controls to evaluate the associations of CCN1 polymorphisms with CHD risk. Our results showed that the protective alleles rs3753793-C (OR = 0.59, 95% CI = 0.42–0.81, P = 0.001), rs2297141-A (OR = 0.66, 95% CI = 0.49–0.90, P = 0.001), and C-A haplotype of rs3753793-rs2297141 (OR = 0.58, 95% CI = 0.42–0.82, P = 0.002) were significantly associated with a decreased atrial septal defect (ASD) risk. Further subgroup analysis in different geography populations revealed robust association of SNP rs2297141 with ASD risk in a Han population residing in high altitude of 2500–4287 m. We also found that the frequency of protective alleles was higher in high-altitude population, and the alleles were responsible for the difference of oxygen physiology–related erythrocyte parameters in different high-altitude populations. rs3753793-C and rs2297141-A are likely related to high altitude and hypoxia adaptation, which may also be the reason for the association between CCN1 polymorphism and ASD risk.

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Data availability

The datasets generated for this study are available from the corresponding author on reasonable request.

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Acknowledgements

We express our appreciation to the original DNA donors who made this study possible.

Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 31670379 and 31660112) and the Program for Innovation and Entrepreneurship of Lanzhou University Students (grant number 20190060166).

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Authors and Affiliations

  1. Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China

    Wenke Yang, Xinyu Song, Shasha Zhang, Nana Chen, Zhenglin Li & Xiaodong Xie

  2. Gansu Cardiovascular Institute, People’s Hospital of Lanzhou City, Lanzhou, China

    Wenke Yang, Dingxiong Xie & Xiaodong Xie

  3. Department of Hematology, Gansu Provincial Key Laboratory of Hematology, Second Hospital of Lanzhou University, Lanzhou, China

    Jun Bai

  4. Department of Cardiac Surgery, Gansu Provincial Hospital, Lanzhou, China

    Tao You & Kang Yi

  5. Genetics Medicine Center, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China

    Xiaodong Xie

Authors
  1. Wenke Yang
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  2. Jun Bai
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  3. Xinyu Song
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  4. Shasha Zhang
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  7. Kang Yi
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  8. Zhenglin Li
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  9. Dingxiong Xie
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  10. Xiaodong Xie
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Contributions

XX, DX, and WY designed the study. WY, JB, TY, and KY enrolled the samples and clinical data. WY, JB, XS, and SZ performed the experiments. WY, JB, XS, SZ, NC, and ZL participated in data analysis. WY drafted the manuscript. XX revised the manuscript critically. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiaodong Xie.

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Ethics approval

This study was approved by the Ethics Committees of Lanzhou University of Basic Medical Science (20160204). The patients/participants provided their written informed consent to participate in this study.

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Written informed consent to participate in this study was provided by the participants or participants’ legal guardian.

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The authors declare no competing interests.

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Responsible editor: Lotfi Aleya

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Yang, W., Bai, J., Song, X. et al. CCN1 gene polymorphisms associated with congenital heart disease susceptibility in Northwest Chinese population from different high-altitude areas. Environ Sci Pollut Res 28, 56927–56937 (2021). https://doi.org/10.1007/s11356-021-14428-x

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