Abstract P145: Associations Of Corin Protein And Its Coding Gene Methylation With Hypertension In Chinese Adults: A Mediation Analysis In The Gusu Cohort

Abstract

Hypothesis: Corin protein, a physiological activator of the atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Its coding gene methylation may be involved in the underlined mechanisms but with no evidence. Objectives: We aimed to examine 1) whether CORIN gene methylation was associated with hypertension and 2) whether this association was mediated by corin protein. Methods: As illustrated in the following picture, peripheral blood DNA methylation of CORIN promoter was quantified by targeted bisulfite sequencing in 2,498 community members (mean aged 53 years, 38% men) as a discovery sample and 1,771 independent participants (mean aged 62 years, 54% men) as a replication sample. We constructed a causal mediation model with DNA methylation as the predictor variable, serum corin as the mediator variable, and blood pressure as the outcome variable, adjusting for age, sex, education level, cigarette smoking, alcohol consumption, obesity, fasting glucose, lipids, and antihypertensive medications. Multiple testing was controlled by adjusting for the total number of CpG loci tested. Results: Of the 9 CpG loci assayed, hyper-methylation methylation of 8 CpGs was significantly associated with lower systolic blood pressure in the discovery sample and 7 associations were also significant in the replication sample (all FDR-adjusted P <0.05). Of the 8 significant CpGs, DNA methylation at only one CpG locus (located at Chr4:47839981) was significantly associated with serum corin (β=-0.003, P =0.038). Serum corin mediated approximately 2.45% (95%CI: 0.05%-7.00%, P =0.046), 7.15% (95%CI: 0.60%-28.00%, P =0.036), and 6.37% (95%CI: 0.10%-42.00%, P =0.048) of the negative associations of hyper-methylation at this CpG site with systolic blood pressure, diastolic blood pressure, and hypertension, respectively. Conclusions: Hyper-methylation at CORIN promoter is associated with hypertension, at least partially through suppressing corin expression or excretion.