Lipids & metabolic liver disease
Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease
Authors' conclusion
The polymorphism rs738409 in the PNPLA3 gene, T2D, and older age were independent predictors of high-risk MASLD.
Study context
- Population
- MASLD patients in tertiary care hepatology practices with polymorphism and liver fibrosis/NIT data; 52 ± 13 years, 46 % male, BMI 36.6 ± 9.9, 35 % T2D
- Participants
- 2,289 patients
- Exposure
- PNPLA3-rs738409 CG/GG vs CC genotype
- Outcome
- High-risk NITs and histologic fibrosis by PNPLA3-rs738409 genotype
Methodological detailstertiary care hepatology practices
- Tertiary care hepatology practices
Main finding
As reported in the abstract
CG/GG vs CCOdds ratio (95 % CI)
High ELF; independent association
3.25(2.03–5.20)
High FIB-4; independent association
2.75(1.90–3.98)
High LSM; independent association
2.71(1.60–4.59)
Advanced histologic fibrosis; independent association
2.56(1.81–3.62)
Observational data: associations, not effects.
Further findings
Genotype frequencies
- High-risk allele at PNPLA3 rs738409
- 53 %
- High-risk allele at MBOAT7 rs641738
- 70 %
- High-risk minor allele at TM6SF2 rs58542926
- 18 %
- Low-risk minor allele at HSD17b13 rs62305723
- 11 %
- PNPLA3-rs738409 CC / CG / GG
- 47 % / 40 % / 13 %
Subgroup with T2D
- Similar associations of PNPLA3-rs738409 with non-invasive tests (NITs) (n = 799)
- all p < 0.05
Original publication
Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease. Diabetes Res Clin Pract. Published 13 December 2024. doi:10.
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