Key result
The GCKR rs1260326 polymorphism was significantly associated with NAFLD risk (OR 0.69; 95% CI 0.54-0.89; P=0.004), with 12.7% of this association mediated by triglyceride levels.
Why the study?
The association between variants in APOC3, GCKR, and PNPLA3 and NAFLD, and whether it correlated to clinical parameters, remained unclear in the Chinese Han elderly population.
Case-Control (n=1,557)
Odds Ratio: 0.69 (95% CI 0.54–0.89)
p-value: p=0.004
No immediate clinical implications for NAFLD; leaves open causal role of rs1260326 for prospective validation.
Background: Accumulated studies have pointed out the striking association between variants in or near APOC3, GCKR, PNPLA3, and nonalcoholic fatty liver disease (NAFLD) at various ages from multiple ethnic groups. This association remained unclear in the Chinese Han elderly population, and whether this relationship correlated to any clinical parameters was also unclear. Objectives: This study aims to decipher the complex relevance between gene polymorphisms, clinical parameters, and NAFLD by association study and mediation analysis. Methods: Eight SNPs (rs2854116, rs2854117, rs780093, rs780094, rs1260362, rs738409, rs2294918, and rs2281135) within APOC3, GCKR, and PNPLA3 were genotyped using the MassARRAY® platform in a large Chinese Han sample comprising of 733 elderly NAFLD patients and 824 age- and ethnic-matched controls. Association and mediation analysis were employed by R. Results: The genotypic frequencies of rs1260326 and rs780094 were significantly different between NAFLD and control (rs1260326: P=0.004, Pcorr=0.020, OR [95%CI]= 0.69 [0.54-0.89]; rs780094: P=0.005, Pcorr=0.025, OR [95%CI]= 0.70 [0.55-0.90]). Particularly, an increased triglyceride level was observed in carriers of rs1260326 T allele (1.94±1.19 mmol/L) compared with non-carriers (1.73±1.05 mmol/L).no significant results were observed in rs780094. Notably, triglyceride levels had considerably indirect impacts on association between NAFLD and rs1260326 (β =0.01, 95% CI: 0.01–0.02), indicating that 12.7% of the association of NAFLD with rs1260326 was mediated by triglyceride levels. Conclusions: Our results identified a prominent relationship between GCKR rs1260326 and NAFLD, and highlighted the mediated effect of triglyceride levels on the that association in the Chinese Han elderly.
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Yuan et al. (2022) conducted a case-control in Nonalcoholic fatty liver disease (NAFLD) (n=1,557). GCKR rs1260326 polymorphism vs. Controls was evaluated on Nonalcoholic fatty liver disease (NAFLD) (OR 0.69, 95% CI 0.54-0.89, p=0.004). The GCKR rs1260326 polymorphism was significantly associated with NAFLD risk (OR 0.69; 95% CI 0.54-0.89; P=0.004), with 12.7% of this association mediated by triglyceride levels.
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