rs34861192

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.

This association study analyzed four T2D-related SNPs (rs5219, rs1801282, rs7903146, rs12255372) in 26 Yakut patients with type 2 diabetes via pyrosequencing. No statistically significant differences were found between Yakut T2D cases and control groups for KCNJ11, PPARG, or TCF7L2 polymorphisms. The study identified strong linkage disequilibrium between TCF7L2 rs7903146 and rs12255372 (D'=1, LOD=4.92) in Yakuts and demonstrated that the risk T-allele frequency of TCF7L2 SNPs is notably lower in Asian populations (3.8% in Yakuts, 2-3% in Japanese and Chinese) compared to European and African populations.

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.