rs1801278

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.

Case-control study of 100 metabolic syndrome patients and 31 controls found IRS-1 G972R (rs1801278) and IRS-2 polymorphisms associated with metabolic syndrome (p<0.0001 and p=0.0001 respectively), but no correlations between these variants and individual MetS components including blood pressure, triglycerides, or HDL/LDL cholesterol levels.

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.

This case-cohort study of 704 postmenopausal women examined 33 SNPs in IGF-I, insulin resistance, and related signaling pathway genes. Six SNPs in INS, IGF-I, and IGFBP3 genes and 11 SNPs in IRS1 and AKT1/2 genes were associated with colorectal cancer risk, with associations differing by obesity status, physical activity, and exogenous estrogen use. Approximately 30-50% of the SNP-cancer association was mediated or influenced by IGF-I/IR traits, suggesting gene-lifestyle interactions affect postmenopausal CRC risk.

This replication study confirms that the TRIB3 Q84R polymorphism (rs2295490) is associated with impaired glucose regulation in three independent samples of European Italians (n=791, n=374, n=394). R84 carriers showed increased risk of impaired glucose regulation (OR 1.54, p=0.004 in sample 1; OR 1.63, p=0.027 in sample 2) and reduced insulin sensitivity measured by glucose clamp (38.8±17.7 vs 31.6±13.3 μmol/min/kg, p=0.022). The association with glucose homeostasis appears to be primarily mediated by altered disposition index (reduced early-phase insulin secretion adjusted for insulin sensitivity) rather than insulin sensitivity alone.

This comprehensive review examines genetic associations in type I interferon-related signaling pathways across multiple autoimmune diseases. The authors review evidence linking dysregulated interferon alpha (IFNα) signaling to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune conditions, identifying multiple susceptibility genes including IFIH1, IRF5, STAT4, TYK2, BLK, BANK1, FCGR2A, and TREX1 with well-replicated associations and functional relevance to IFN pathway dysfunction.