Longitudinal genome-wide methylation study of Roux-en-Y gastric bypass patients reveals novel CpG sites associated with essential hypertension

Adrian E. Boström, Jessica Mwinyi, Sarah Voisin, Wenting Wu, Bernd Schultes, Kang Zhang, Helgi B. Schiöth

Essential hypertension is a significant risk factor for cardiovascular diseases. Emerging research suggests a role of DNA methylation in blood pressure physiology. We aimed to investigate epigenetic associations of promoter related CpG sites to essential hypertension in a genome-wide methylation approach. The genome-wide methylation pattern in whole blood was measured in 11 obese patients before and six months after Roux-en-Y gastric bypass surgery using the Illumina 450 k beadchip. CpG sites located within 1500 bp of the transcriptional start site of adjacent genes were included in our study, resulting in 124 199 probes investigated in the subsequent analysis. Percent changes in methylation states and SBP measured before and six months after surgery were calculated. These parameters were correlated to each other using the Spearman's rank correlation method (Edgeworth series approximation). To further investigate the detected relationship between candidate CpG sites and systolic blood pressure levels, binary logistic regression analyses were performed in a larger and independent cohort of 539 individuals aged 19-101 years to elucidate a relationship between EH and the methylation state in candidate CpG sites. We identified 24 promoter associated CpG sites that correlated with change in SBP after RYGB surgery (p < 10(-16)). Two of these CpG loci (cg00875989, cg09134341) were significantly hypomethylated in dependency of EH (p < 10(-03)). These results were independent of age, BMI, ethnicity and sex. The identification of these novel CpG sites may contribute to a further understanding of the epigenetic regulatory mechanisms underlying the development of essential hypertension.