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Abstract #0416

PNPLA3 Gene Polymorphisms Affect MASLD Progression Severity Assessed by MRE in a Large Cohort of Clinical Patients

Peng Xu1, Shulan Tian2, Caixin Qiu1, Hao Wu1, Jiahui Li1, Eric W. Klee2, Alina M. Allen3, Richard L. Ehman1, and Meng Yin1
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, 2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States, 3Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States

Synopsis

Keywords: Liver, Elastography, Liver Stiffness, Gene Polymorphisms

Motivation: Understanding how liver stiffness (LS), which indicates liver disease severity, varies across PNPLA3 alleles and polygenic risk scores (PRS) may improve MASLD patient management.

Goal(s): To analyze the association between PNPLA3 variants/PRS and LS distribution, and to assess their role in LS-based risk stratification for liver outcomes.

Approach: Logistic regression analyzed PNPLA3 genotype associations with MRE-defined liver outcomes, while linear regression evaluated continuous LS with PNPLA3 alleles or PRS.

Results: For genotypes CG and GG versus CC, the odds ratios were 1.9 and 2.4 for advanced fibrosis, 1.6 and 3.0 for cirrhosis, and 2.2 and 3.1 for decompensated cirrhosis, respectively.

Impact: Genotype impacts liver stiffness, thus understanding their association is essential for improving MASLD prevention, prognosis, and treatment. Integrating genetic risk and LS assessment could enhance risk prediction for liver complications.

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