How the PNPLA3 gene affects who gets fatty liver and who is protected

PNPLA3 in Susceptibility and Resistance to Fatty Liver Disease

NIH-funded research Ut Southwestern Medical Center · NIH-11138627

This research looks at how changes in the PNPLA3 gene influence the chance of developing alcoholic and nonalcoholic fatty liver disease across people of different ancestries.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUt Southwestern Medical Center NIH-funded
Lab location1 site (Dallas, United States)
Project IDNIH-11138627 on NIH RePORTER

What this research studies

We're studying how common changes in the PNPLA3 gene make some people more likely and others more resistant to fatty liver disease. Using human genetic data from the Dallas Heart Study and other cohorts, the team links specific PNPLA3 variants (such as the risk 148M and the protective S453I) to differences in liver fat and ancestry-related risk. They pair those human findings with laboratory work and mouse experiments to uncover the molecular and metabolic pathways by which these variants act. The aim is to identify targets or strategies that could lead to new treatments or prevention approaches tailored to PNPLA3 biology.

Who could benefit from this research

Good fit: Adults with or at risk for alcoholic or nonalcoholic fatty liver disease—particularly individuals of Hispanic, European, or African ancestry—would be most relevant to this work.

Not a fit: People whose liver disease stems from unrelated causes (for example, chronic viral hepatitis or rare inherited metabolic disorders) may not directly benefit from PNPLA3-focused findings.

Why it matters

Potential benefit: If successful, this work could point to new prevention methods or targeted treatments for fatty liver based on a person's PNPLA3 genetic type.

How similar studies have performed: Previous human genetic studies identified PNPLA3 variants that strongly predict liver fat, and mouse proof-of-concept experiments have shown modulation of the variant's effects, though clinically approved therapies targeting PNPLA3 are not yet established.

Where this research is happening

Dallas, 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.
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.