rs2854117

This variant is located in the APOC3 gene.

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

triglyceride measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.05
p 8.0e-99
N 394,642
Large GWAS
European

fatty acid amount

Sun Y et al. “GWAS and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating fatty acids.” Hgg Advances 6(4):100470 (2025)
Allele T
OR —
p 2.0e-39
N 239,268
Large GWAS
European
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Research that mentions this SNP (4)

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Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B
ReviewMauro Viganò et al.(2013)· Hepatology

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.

Traits studied:Cardiovascular diseaseChronic kidney diseaseCirrhosisHepatic injuryHepatic steatosisHepatocellular carcinomaInsulin resistanceLipid metabolismLiver fibrosisMetabolic syndromeNecroinflammationNonalcoholic fatty liver disease (NAFLD)Nonalcoholic steatohepatitis (NASH)ObesityType 2 diabetes
PubMedDOIMetascience Observatory
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A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population
AssociationN=470Verrijken A. et al.(2013)· Obesity

A cross-sectional study of 470 obese patients found that PNPLA3 variant rs738409 (I148M) was significantly associated with non-alcoholic steatohepatitis (NASH) and severity of necroinflammatory changes (steatosis, lobular inflammation, ballooning) independently of metabolic factors and BMI. Conversely, the APOC3 variant rs2854117 showed no significant associations with liver histology or metabolic parameters of NAFLD.

Traits studied:Hepatic ballooningLiver fibrosisLiver steatosisLobular inflammationNon-alcoholic fatty liver disease (NAFLD)Non-alcoholic steatohepatitis (NASH)Serum liver enzymes (ALT, AST)
PubMedDOIMetascience Observatory
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Variant in the glucokinase regulatory protein ( GCKR ) gene is associated with fatty liver in obese children and adolescents
AssociationN=455Nicola Santoro et al.(2012)· Hepatology

This association study examined 455 obese children and adolescents (181 Caucasians, 139 African Americans, 135 Hispanics) and found that rs1260326 in GCKR is associated with hepatic fat accumulation and elevated triglycerides/large VLDL levels across all ethnic groups (p=0.034-0.00002). The PNPLA3 rs738409 variant also associated with hepatic fat content. Jointly, these variants explained 32% of hepatic fat variance in Caucasians, 39% in African Americans, and 15% in Hispanics.

Traits studied:Hepatic fat accumulationHepatic steatosisLarge VLDLNon-alcoholic fatty liver diseaseTriglycerides
PubMedDOIMetascience Observatory
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Dissociation betweenAPOC3variants, hepatic triglyceride content and insulin resistance
ReviewJulia Kozlitina et al.(2011)· Hepatology

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.

Traits studied:Alcoholic liver diseaseCardiovascular diseaseChronic kidney diseaseHCCHepatic steatosisHepatic triglyceridesHepatitis B steatosisHepatitis C progressionHepatocellular carcinomaInsulin resistanceLipid metabolismLiver fat contentLiver fibrosisNAFLDNASHNecroinflammationNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisType 2 diabetes
PubMedDOIMetascience Observatory

About APOC3

This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

View all APOC3 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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