rs1800804

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.

This functional study examined the impact of three common MTTP promoter polymorphisms (rs1800804 -164T>C, rs1800803 -400A>T, rs1800591 -493G>T) on gene expression and LDL cholesterol levels. The common haplotype -164T/-400A/-493G showed approximately twofold lower promoter activity than the rare -164C/-400T/-493T haplotype in hepatic cells, with the -164T>C variant playing a key role. EMSA revealed differential SREBP1a transcription factor binding to the -164 region, explaining functional differences in MTTP expression.