rs3745367

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 genome-wide association study identified two SNPs (rs3745367 and rs1423096) in the RETN gene associated with circulating resistin levels in Han Chinese hypertensive subjects. Using Mendelian randomization in an independent cohort (CVDFACTS), rs1423096 was significantly associated with metabolic syndrome risk (OR=2.21, p=0.0034) and type 2 diabetes mellitus (OR=1.62, p=0.0063), providing evidence that resistin causally contributes to T2DM development.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

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 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.