Key result
PNPLA3 variant linked to greater LV mass index only in steatotic liver disease.
Why the study?
Steatotic liver disease is associated with cardiovascular disease, and PNPLA3 rs738409C>G determines liver fat accumulation, but its association with cardiac structure and function remains unclear.
Does the PNPLA3 rs738409C>G variant affect cardiac remodeling in young adults with and without steatotic liver disease?
Cohort (n=657)
No
Does the PNPLA3 rs738409C>G variant affect cardiac remodeling in young adults with and without steatotic liver disease?
The PNPLA3 rs738409C>G variant is associated with subclinical adverse cardiac remodeling in young adults, but only in the presence of steatotic liver disease.
May indicate PNPLA3–steatotic liver disease interaction on remodeling; hypothesis-generating and should not yet change practice.
Steatotic liver disease (SLD) is associated with cardiovascular disease. The PNPLA3 rs738409C>G variant is a genetic determinant of liver fat accumulation. We investigated the association of the PNPLA3 rs738409C>G variant with cardiac structure and function in young adults, stratified by SLD status. Participants underwent genotyping at 17 years and liver and cardiac magnetic resonance imaging at 27 years. SLD was defined as volumetric liver fat fraction >3.55%. PNPLA3 rs738409 was analyzed primarily using a dominant genetic model (CC vs. CG/GG). Multivariable linear regression was used to evaluate the association between PNPLA3 rs738409C>G and cardiac parameters. Of 657 participants, 38.1% carried PNPLA3 rs738409C>G and 16.4% had SLD. Associations between PNPLA3 rs738409C>G and cardiac parameters were contingent on SLD status, with significant PNPLA3 × SLD interactions observed for left ventricular mass index (LVMi; p = 0.009), left ventricular end-diastolic volume index (LVEDVi; p = 0.015), and right ventricular end-diastolic volume index (RVEDVi; p = 0.049). PNPLA3 rs738409C>G was associated with greater LVMi (p = 0.014), LVEDVi (p = 0.005), and RVEDVi (p = 0.040) among individuals with SLD, but not without SLD. In this non-mechanistic observational study, PNPLA3 rs738409C>G was associated with subclinical cardiac remodeling only in the presence of SLD. These hypothesis-generating findings and any potential mechanisms require confirmation in future studies.
No takes yet. Share an insight, caveat, or question.
Lan et al. (2026) conducted a cohort in Steatotic liver disease and cardiac remodeling (n=657). PNPLA3 rs738409C>G variant vs. PNPLA3 wild-type (CC) was evaluated on Left ventricular mass index (LVMi) in individuals with steatotic liver disease (β 3.29, 95% CI 0.68-5.90, p=0.014). The PNPLA3 rs738409C>G variant was associated with greater left ventricular mass index (β 3.29) and end-diastolic volumes only in the presence of steatotic liver disease.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: