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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2781-2790
Number of pages10
JournalDiabetologia
Volume58
Issue number12
DOIs
Publication statusPublished - 24-09-2015

Fingerprint

Resistin
DNA Methylation
Genetic Promoter Regions
Single Nucleotide Polymorphism
Genes
Monocytes
Messenger RNA
Genome
Epigenomics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Nakatochi, Masahiro ; Ichihara, Sahoko ; Yamamoto, Ken ; Ohnaka, Keizo ; Kato, Yosuke ; Yokota, Shigeki ; Hirashiki, Akihiro ; Naruse, Keiko ; Asano, Hiroyuki ; Izawa, Hideo ; Matsubara, Tatsuaki ; Yokota, Mitsuhiro. / 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. In: Diabetologia. 2015 ; Vol. 58, No. 12. pp. 2781-2790.
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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 = "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.",
author = "Masahiro Nakatochi and Sahoko Ichihara and Ken Yamamoto and Keizo Ohnaka and Yosuke Kato and Shigeki Yokota and Akihiro Hirashiki and Keiko Naruse and Hiroyuki Asano and Hideo Izawa and Tatsuaki Matsubara and Mitsuhiro Yokota",
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Nakatochi, M, Ichihara, S, Yamamoto, K, Ohnaka, K, Kato, Y, Yokota, S, Hirashiki, A, Naruse, K, Asano, H, Izawa, H, Matsubara, T & Yokota, M 2015, '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', Diabetologia, vol. 58, no. 12, pp. 2781-2790. https://doi.org/10.1007/s00125-015-3763-9

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

In: Diabetologia, Vol. 58, No. 12, 24.09.2015, p. 2781-2790.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Nakatochi, Masahiro

AU - Ichihara, Sahoko

AU - Yamamoto, Ken

AU - Ohnaka, Keizo

AU - Kato, Yosuke

AU - Yokota, Shigeki

AU - Hirashiki, Akihiro

AU - Naruse, Keiko

AU - Asano, Hiroyuki

AU - Izawa, Hideo

AU - Matsubara, Tatsuaki

AU - Yokota, Mitsuhiro

PY - 2015/9/24

Y1 - 2015/9/24

N2 - 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.

AB - 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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U2 - 10.1007/s00125-015-3763-9

DO - 10.1007/s00125-015-3763-9

M3 - Article

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SP - 2781

EP - 2790

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 12

ER -