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01.12.2015 | Article

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

verfasst von: Masahiro Nakatochi, Sahoko Ichihara, Ken Yamamoto, Keizo Ohnaka, Yosuke Kato, Shigeki Yokota, Akihiro Hirashiki, Keiko Naruse, Hiroyuki Asano, Hideo Izawa, Tatsuaki Matsubara, Mitsuhiro Yokota

Erschienen in: Diabetologia | Ausgabe 12/2015

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Abstract

Aims/hypothesis

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/interpretation

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.

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Titel: 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
verfasst von: Masahiro Nakatochi
Sahoko Ichihara
Ken Yamamoto
Keizo Ohnaka
Yosuke Kato
Shigeki Yokota
Akihiro Hirashiki
Keiko Naruse
Hiroyuki Asano
Hideo Izawa
Tatsuaki Matsubara
Mitsuhiro Yokota
Publikationsdatum: 01.12.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 12/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-015-3763-9

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