title: Modulation of blood pressure in response to low ambient temperature: The role of DNA methylation of zinc finger genes.
abstract: BACKGROUND
  Blood 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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  With 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%).
  
  
  CONCLUSIONS
  Methylation changes in ZNF genes might be involved in the elevation of blood pressure when the body is exposed to cold temperature.
authors.affiliation: Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Changwoo
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Preventive Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Sanghyuk
authors.initials: S
authors.lastname: Bae
authors.affiliation: Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: ychong1@snu.ac.kr.
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D056910:Republic of Korea; D012621:Seasons; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C524688:ZKSCAN4 protein, human; C464650:ZNF23 protein, human; C000619273:ZNF595 protein, human; C000619298:ZNF597 protein, human; C568525:ZNF668 protein, human
keywords: Blood pressure; DNA methylation; Elderly; Epigenetic processes; Temperature