Key result
APOC3 gene polymorphisms linked to ~80% higher MASLD risk, mediated by triglycerides.
Why the study?
Relationships between single nucleotide polymorphisms in the APOC3 and ANGPTL8 genes and MASLD remain controversial.
Do APOC3 and ANGPTL8 gene polymorphisms increase the risk of MASLD in a Chinese population?
Case-Control (n=440)
Do APOC3 and ANGPTL8 gene polymorphisms increase the risk of MASLD in a Chinese population?
APOC3 gene polymorphisms are associated with an increased risk of MASLD in the Chinese population, an effect largely mediated by triglyceride levels.
TG may mediate APOC3/ANGPTL8 SNP-MASLD links; leaves open causality and clinical adoption pending prospective studies.
Apolipoprotein C3 (APOC3) and angiopoietin-like protein 8 (ANGPTL8) genes are related to lipid metabolism. The relationships between single nucleotide polymorphisms (SNPs) in the APOC3 and ANGPTL8 genes with metabolic dysfunction-associated steatotic liver disease (MASLD) remain controversial. This study aimed to investigate the associations between specific SNPs in the APOC3 and ANGPTL8 genes and MASLD risk, with a particular focus on the mediating role of triglycerides (TG). A total of 440 participants were enrolled and categorised into MASLD and control groups. Genotyping of APOC3 SNPs (rs5128, rs2854116 and rs2854117) and ANGPTL8 SNP (rs2278426) was conducted using polymerase chain reaction-restriction fragment length polymorphism or Sanger sequencing methods. Multivariate logistic regression was employed to estimate the associations between these SNPs and MASLD risk, and mediation analysis was performed to assess the potential mediating effect of TG. We found that APOC3 SNPs were associated with MASLD risk, with increased odds ratios (ORs) indicating a higher risk of MASLD: rs5128 CG + GG genotype (OR = 1.8, 95% CI = 1.1-2.8), rs2854116 TC + CC genotype (OR = 1.9, 95% CI = 1.1-3.1) and rs2854117 CT + TT genotype (OR = 1.9, 95% CI = 1.2-3.2). No association was found between ANGPTL8 rs2278426 and MASLD (p > 0.05). Mediation analysis revealed that TG significantly mediated these relationships, accounting for 80.25% of the effect for rs5128, 64.61% for rs2854116 and 62.59% for rs2854117. In summary, polymorphisms in APOC3 (rs5128, rs2854116 and rs2854117) were associated with MASLD risk, with TG serving as a potential mediating factor. In contrast, ANGPTL8 rs2278426 polymorphism did not show any association with MASLD.
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Pan et al. (2025) conducted a case-control in Metabolic dysfunction-associated steatotic liver disease (MASLD) (n=440). APOC3 gene polymorphisms (rs5128, rs2854116, rs2854117) vs. Wild-type genotypes was evaluated on MASLD risk associated with APOC3 rs5128 CG + GG genotype (OR 1.8, 95% CI 1.1-2.8). APOC3 gene polymorphisms were associated with a higher risk of MASLD (e.g., rs5128 OR 1.8; 95% CI 1.1-2.8), with triglycerides significantly mediating this effect.
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