title: Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites.
abstract: OBJECTIVE
  To investigate epigenetic regulation of the plasma concentration of resistin, we performed an epigenome-wide association study for this variable and DNA methylation (DNAm) in an elderly Japanese cohort and then assessed the relation of single nucleotide polymorphisms (SNPs) associated with the plasma resistin concentration to DNAm level at identified sites.
  
  
  METHODS
  The association of plasma resistin level with DNAm status was examined in 191 nondiabetic elderly men with the Illumina Infinium HumanMethylation450 BeadChip array. The association between DNAm status at specific sites in the flanking region of the resistin gene (RETN) and RETN mRNA abundance was then evaluated with a public data set for 1202 monocyte samples from a multi-ethnic cohort. Finally, the association of DNAm status and SNPs in the promoter region of RETN was assessed in two cohorts comprising a total of 478 Japanese individuals.
  
  
  RESULTS
  DNAm status at cg02346997 located in the RETN promoter region showed a negative genome-wide significant association with the plasma resistin level (p = 6.02 × 10(-10)). Four DNAm sites in the RETN promoter region including cg02346997 (p = 4.23 × 10(-70)) showed a negative genome-wide significant association with RETN mRNA abundance in monocytes. Furthermore, the number of minor alleles of the RETN promoter SNPs rs34861192 and rs3219175 was negatively associated with DNAm level at cg02346997 (p = 4.43 × 10(-17)).
  
  
  CONCLUSIONS
  Our results suggest that RETN promoter SNPs might influence the circulating resistin level through an effect on DNAm at cg02346997 and on RETN mRNA abundance in monocytes.
authors.affiliation: Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakatochi
authors.affiliation: Graduate School of Regional Innovation Studies, Mie University, Tsu, Japan.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.affiliation: Department of Medical Chemistry, School of Medicine, Kurume University, Kurume, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.affiliation: Department of Registered Dietitians, Faculty of Health and Welfare, Tokai Gakuin University, Kakamigahara, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Internal Medicine, Iwakura Hospital, Iwakura, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirashiki
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.affiliation: Department of Internal Medicine, Iwakura Hospital, Iwakura, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Asano
authors.affiliation: Department of Cardiology, Fujita Health University Banbuntane Hotokukai Hospital, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Genome Science, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan. myokota@dpc.aichi-gakuin.ac.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D052243:Resistin / Q000235:genetics* / Q000378:metabolism*
chemical_list: C499624:RETN protein, human; D052243:Resistin
keywords: Cohort study; DNA methylation; Epigenetics; Epigenome-wide association study; Resistin; Single nucleotide polymorphism