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Original research
Association between CORIN methylation and hypertension in Chinese adults
  1. Jijun Shi1,
  2. Lei Wu2,
  3. Yan Chen3,
  4. Mingzhi Zhang4,
  5. Jia Yu5,
  6. Liyun Ren4,
  7. Yan He4,
  8. Jing Li5,
  9. Shengqi Ma5,
  10. Weidong Hu1,
  11. Hao Peng5
  1. 1Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China
  2. 2Department of Maternal and Child Health, Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou, Jiangsu, China
  3. 3Department of Nephrology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, China
  4. 4Department of Epidemiology, Soochow University Medical College, Suzhou, China
  5. 5Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases of Soochow University, Suzhou, Jiangsu, China
  1. Correspondence to Dr Hao Peng, Department of Epidemiology, Soochow University Medical College, Suzhou, Jiangsu, China; penghao{at}suda.edu.cn

Abstract

Background Corin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether CORIN gene methylation was involved in the underlying molecular mechanisms.

Methods DNA methylation levels of CORIN were measured by target bisulfite sequencing using genomic DNA isolated from peripheral blood mononuclear cells in 2498 participants in the Gusu cohort (discovery sample) and 1771 independent participants (replication sample). We constructed a mediation model with DNA methylation as the predictor, serum corin as the mediator, and hypertension as the outcome, adjusting for covariates. Multiple testing was controlled by false discovery rate (FDR) approach.

Results Of the 9 CpGs assayed, hypermethylation at all CpGs were significantly associated with a lower level of blood pressure in the discovery sample and eight associations were also significant in the replication sample (all FDR-adjusted p<0.05). Serum corin mediated approximately 3.07% (p=0.004), 6.25% (p=0.002) and 10.11% (p=0.034) of the associations of hypermethylation at one CpG (Chr4:47840096) with systolic and diastolic blood pressure, and hypertension, respectively. All these mediations passed the causal inference test.

Conclusions These results suggest that hypermethylation in the CORIN gene is associated with a lower odds of prevalent hypertension and may be involved in the role of corin in blood pressure regulation.

  • hypertension
  • epidemiology

Data availability statement

Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author at penghao@suda.edu.cn on reasonable request.

http://dx.doi.org/10.1136/pmj-2022-141802

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    Data availability statement

    Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author at penghao@suda.edu.cn on reasonable request.

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    Footnotes

    • JS, LW and YC are joint first authors.

    • JS, LW and YC contributed equally.

    • Contributors JS, WH and HP constructed the conception and design, LW and YC analysed and interpreted the data, JS drafted the paper, MZ, JY, LR, YH, JL and SM collected the data, WH and HP revised and gave the final approval of the version to be published, and all authors agreed to be accountable for all aspects of the work. HP is responsible for the overall content as the guarantor.

    • Funding This study was supported by the National Natural Science Foundation of China (NO. 82173596, 81903384 and 81872690), the Suzhou Municipal Science and Technology Bureau (NO. SKJY2021040 and SYS2020091), the Suzhou Health Personnel Training Project (GSWS2021066), the Jiangsu Province Maternal and Child Health Research Project (F202027), the Suzhou Science and Technology Development Plan (Livelihood Technology) Project (SS202009), the Scientific Research Foundation of the Second Affiliated Hospital of Soochow University (SDFEYGJ2009), and a Project of the Priority Academic Programme Development of Jiangsu Higher Education Institutions.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.