What question did this study set out to answer?

To examine the relationship between the PNPLA3 rs2896019 polymorphism and both susceptibility and severity of MASLD.

April 19, 2026

Patatin-like phospholipase domain-containing protein 3 rs2896019 and MASLD Susceptibility and Severity in Adults: A Systematic Review and Meta-Analysis of Case–Control Studies

Key Points

To examine the relationship between the PNPLA3 rs2896019 polymorphism and both susceptibility and severity of MASLD.
Conducted a systematic search across multiple databases for relevant case-control studies.
Included 10 eligible cohorts with a total of 15,028 participants.
Calculated odds ratios and confidence intervals to assess the association.
Performed subgroup analyses based on diagnostic modalities.
The G allele of rs2896019 is linked to a 51% increased risk of MASLD (OR: 1.5).
A gene-dose effect was demonstrated, with homozygous individuals at even higher risk (OR: 2.32).
Restricting to biopsy-proven cohorts reduced heterogeneity and strengthened the association (OR = 1.91).
The G allele significantly raised the risk of severe MASLD compared to mild steatosis.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of global liver morbidity. Genetic variants, particularly in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, are critical determinants of metabolic traits and disease progression. This study presents the first meta-analysis to clarify the association between the PNPLA3 rs2896019 polymorphism and MASLD susceptibility and severity. We systematically searched PubMed, Embase, Web of Science, and Google Scholar for relevant articles published up to February 12, 2026. Data were extracted, and summary estimates of the association between PNPLA3 rs2896019 and MASLD were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the effect. Ten eligible case-control cohorts involving 15,028 participants (3118 cases and 11,910 controls) were included. Our results demonstrated that the G allele is significantly associated with a 51% increased risk of MASLD (OR: 1.5, CI: 1.23-1.85, P P I2 = 0%) and strengthened the association (OR = 1.91). Furthermore, the G allele significantly increased the risk of severe MASLD/MASH (OR = 2.06) compared to mild steatosis (OR = 1.40). In conclusion, the PNPLA3 rs2896019 G allele is a robust, dose-dependent risk factor for both the development and severe progression of MASLD.

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Cite This Study

Lim et al. (Fri,) studied this question.

synapsesocial.com/papers/69e47321010ef96374d8f02d https://doi.org/https://doi.org/10.1177/15578518261443934

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