Modulation of blood pressure in response to low ambient temperature: The role of DNA methylation of zinc finger genes

Abstract

BackgroundBlood pressure rises with a drop in external temperature, but the role of DNA methylation in such blood pressure modulation has not been studied in detail. We evaluated blood pressure and DNA methylation of vascular disease-related genes in association with low temperature. MethodsTo examine changes in blood pressure and DNA methylation associated with low temperature, we conducted repeated measures analysis among 50 participants over 3 repeated visits, and validated the association among another 52 participants. In addition, the mean of methylation changes in the identified CpG sites was evaluated with changes in blood pressure. Mediation analyses were also conducted to model the indirect association between low ambient temperature and blood pressure through changes in DNA methylation. ResultsWith a 1°C decrease in temperature, increases of 0.6mmHg (standard error (SE), 0.2) in SBP and 0.3mmHg (SE, 0.1) in DBP occurred (P<0.05). Of 24,490 CpG sites in vascular genes, 2 CpG sites of zinc finger (ZNF) genes were significantly associated with temperature after Bonferroni's correction in discovery and replication data. A 10% increase in methylation expression in 2 CpG sites in ZNF genes was associated with a 4-mmHg elevation in DBP (SE, 1.8; P=0.0236). The hypermethylation was attributable to the association of ambient temperature with DBP (proportion of mediation=11.8–20.4%). ConclusionsMethylation changes in ZNF genes might be involved in the elevation of blood pressure when the body is exposed to cold temperature.