Masahiro Nakatochi1, Sahoko Ichihara2, Ken Yamamoto3, Keizo Ohnaka4, Yosuke Kato5, Shigeki Yokota6, Akihiro Hirashiki7, Keiko Naruse8, Hiroyuki Asano6, Hideo Izawa9, Tatsuaki Matsubara8, Mitsuhiro Yokota10. 1. Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan. 2. Graduate School of Regional Innovation Studies, Mie University, Tsu, Japan. 3. Department of Medical Chemistry, School of Medicine, Kurume University, Kurume, Japan. 4. Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5. Department of Registered Dietitians, Faculty of Health and Welfare, Tokai Gakuin University, Kakamigahara, Japan. 6. Department of Internal Medicine, Iwakura Hospital, Iwakura, Japan. 7. Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan. 8. Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan. 9. Department of Cardiology, Fujita Health University Banbuntane Hotokukai Hospital, Nagoya, Japan. 10. 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.
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.
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.
Entities:
Keywords:
Cohort study; DNA methylation; Epigenetics; Epigenome-wide association study; Resistin; Single nucleotide polymorphism
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