Differential methylation in blood pressure control genes is associated to essential hypertension in African Brazilian populations

While genetic studies have provided insights into essential hypertension (EH, defined by high blood pressure ≥140/90 mmHg), investigation through epigenetics may address gaps in understanding its heritability. This study focused on African Brazilian populations in Vale do Ribeira River region, due to their high hypertension prevalence. We aimed to determine if DNA methylation is linked to hypertension susceptibility, through a genome-wide evaluation of 80 peripheral blood samples from normotensive (39) and hypertensive (41) individuals, with Infinium Methylation EPIC BeadChip platform. Data were analyzed using ChAMP package and cross-referenced with information from databases such as EWAS Atlas, GWAS catalog, GeneCards, literature, and tools such as VarElect and EWAS Toolkit. The comparison between hypertensive and normotensive revealed 190 differentially methylated CpG positions (DMPs) and 46 differentially methylated regions (DMRs), both with p-value ≤0.05. Among the DMPs, 27 were found to have a plausible role in blood pressure. Among the DMRs, those mapped to ABAT, BLCAP, CERS3, EIF4E, FMN1, GABBR1, HLA-DQB2, HOXA5, IL5RA, KCNH2, MIR487B, MIR539, MIR886, MKRN3, NUDT12, PON3, RNF39, RWDD3, and TSHBS1 were highlighted because of their lowest p-values, current literature, and/or VarElect prioritization. Our findings suggest that differences in methylation contribute to the high susceptibility to essential hypertension in these populations.尽管遗传学研究已为原发性高血压（essential hypertension, EH，定义为血压≥140/90 mmHg）提供了诸多见解，但表观遗传学层面的探索或可填补学界对其遗传力认知的空白。本研究聚焦于里贝拉河谷地区的巴西非洲裔人群，因该群体高血压患病率居高不下。本研究旨在明确DNA甲基化是否与高血压易感性相关，通过对80例外周血样本开展全基因组甲基化评估，其中血压正常者39例、高血压患者41例，检测采用Infinium甲基化EPIC微珠芯片（Infinium Methylation EPIC BeadChip）平台完成。本研究使用ChAMP软件包（ChAMP package）对数据进行分析，并与EWAS图谱（EWAS Atlas）、全基因组关联研究目录（GWAS Catalog）、GeneCards数据库、已发表文献等数据源，以及VarElect工具、EWAS工具包（EWAS Toolkit）等工具的信息进行交叉比对。通过高血压患者与血压正常者的组间比对，共鉴定出190个差异甲基化CpG位点（differentially methylated CpG positions, DMPs）与46个差异甲基化区域（differentially methylated regions, DMRs），所有位点与区域的P值均≤0.05。在上述DMPs中，有27个位点被推测与血压调控存在潜在关联。在鉴定出的DMRs中，定位于ABAT、BLCAP、CERS3、EIF4E、FMN1、GABBR1、HLA-DQB2、HOXA5、IL5RA、KCNH2、MIR487B、MIR539、MIR886、MKRN3、NUDT12、PON3、RNF39、RWDD3及TSHBS1等基因的区域因P值最低、已有文献支持及/或VarElect工具的优先排序结果而被重点关注。本研究结果表明，甲基化水平差异是该群体原发性高血压高易感性的重要贡献因素。