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.
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 email@example.com on reasonable request.
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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.
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