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.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 r...