rs3745368

This epigenome-wide association study (EWAS) in 192 elderly Japanese men identified DNA methylation site cg02346997 in the RETN promoter region as significantly associated with plasma resistin level (p=6.02×10⁻¹⁰). The study found that RETN SNPs rs34861192 and rs3219175 were negatively associated with methylation at cg02346997 (p=4.43×10⁻¹⁷), suggesting these promoter SNPs influence circulating resistin through effects on DNA methylation and RETN mRNA abundance.

In an aged Japanese cohort of 3,133 participants from the KING study, plasma resistin concentration was significantly associated with two RETN polymorphisms: rs34861192 (the most prominent, explaining 35.9% of variance) and rs3745368. These variants independently determined resistin levels and resistin levels were associated with metabolic traits including dyslipidemia, insulin concentration, and obesity.

This is a letter to the editor commenting on a study of resistin gene SNPs in an aged Japanese population. The authors argue that rs1862513 (SNP-420C>G) should still be considered a promising causal variant for determining plasma resistin levels, despite statistical analyses suggesting rs34861192 (SNP-638G>A) as the stronger determinant. The authors note that functional data supports rs1862513's role through transcription factor binding, and that population-specific allele frequencies and linkage disequilibrium limitations make it difficult to distinguish the causal variant from association statistics alone.

This study examined four non-coding SNPs in the resistin gene (RETN) for association with Type 2 diabetes and related traits in a Finnish cohort of 781 diabetes cases and 409 controls. While the SNPs showed no significant association with Type 2 diabetes itself, the common CCG haplotype (rs1862513-rs3219177-rs3745367) was associated with increased weight, waist circumference, and diastolic blood pressure in cases, lower insulin sensitivity in spouse controls, and rs3745368 was associated with lower HDL cholesterol. The findings provide evidence that resistin gene variants are related to obesity and insulin resistance phenotypes.