Dual Effects of a RETN Single Nucleotide Polymorphism (SNP) at -420 on Plasma Resistin: Genotype and DNA Methylation
Context:We previously reported that SNP (single nucleotide polymorphism) -420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of CpG dinucleotides.Objecti...
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Published in | The journal of clinical endocrinology and metabolism Vol. 102; no. 3; pp. 884 - 892 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Endocrine Society
01.03.2017
Copyright Oxford University Press Oxford University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Context:We previously reported that SNP (single nucleotide polymorphism) -420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of CpG dinucleotides.Objective:To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420.Design and Methods:Genomic DNA was extracted from peripheral white blood cells in 2,078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after the bisulfite conversion of DNA.Results:Methylation at SNP-420 was highest in the C/C genotype (36.9±5.7%), followed by C/G (21.4±3.5%) and G/G (2.9±1.4%) (P<0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in C/C (β= -0.134, P< 0.001) or C/G (β=-0.227, P<0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC decreased the methylation at SNP-420, and increased RETN mRNA. SNP+1263 (rs3745369), located in the 3’ untranslated region of RETN, was also associated with methylation at SNP-420. In addition, hs-CRP (highly-sensitive C-reactive protein) was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body-mass index was positively associated.Conclusions:Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic, effects on plasma resistin. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jc.2016-2417 |