PNPLA3-148M gene change and alcohol-related liver damage

The pathophysiological function of PNPLA3-148M variant in alcohol-induced liver injury

NIH-funded research Indiana University Indianapolis · NIH-11325419

This work looks at how a common gene change called PNPLA3-148M may make people who drink alcohol more likely to get liver inflammation and scarring.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionIndiana University Indianapolis NIH-funded
Lab location1 site (Indianapolis, United States)
Project IDNIH-11325419 on NIH RePORTER

What this research studies

From my point of view as a patient, the researchers are using mice engineered to carry the human PNPLA3-148M change and lab-grown liver cells to see how the mutation affects fat handling, inflammation, and scarring after alcohol exposure. They will compare mice with the normal and 148M versions and study molecular signals in liver cells to find what goes wrong. The team aims to tie the 148M change to specific pathways that drive alcohol-related liver injury. This work is lab- and animal-based and is intended to reveal mechanisms that could guide future tests or treatments for people with alcohol-related liver disease.

Who could benefit from this research

Good fit: People who drink alcohol and have or are at risk for alcohol-related liver disease, especially those who carry the PNPLA3-148M gene variant, would be most relevant to this research.

Not a fit: People whose liver disease comes from non-alcohol causes (for example viral hepatitis or autoimmune liver disease) or lifelong non-drinkers are less likely to benefit directly from these findings.

Why it matters

Potential benefit: If successful, this work could explain why some drinkers develop severe liver disease and point to targets for prevention or new treatments.

How similar studies have performed: Large genetic studies have repeatedly linked PNPLA3-148M to fatty liver and earlier mouse models have provided clues, but the precise mechanisms in alcohol-driven inflammation and fibrosis are still not fully worked out.

Where this research is happening

Indianapolis, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Alcoholic Liver Diseases
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.