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PNPLA3 encodes a lipase enzyme that breaks down triglycerides stored in liver cells. Certain variants impair this process, increasing susceptibility to non-alcoholic fatty liver disease (NAFLD), particularly with high-calorie or high-fructose diets.
Regulates triglyceride metabolism and lipid droplet remodeling in hepatocytes (liver cells) and adipose tissue.
The I148M variant (rs738409) is the most studied PNPLA3 polymorphism linked to liver fat accumulation.
| Genotype | Impact | What it means |
|---|---|---|
| CC (Normal) | Low impact | Normal PNPLA3 enzyme activity. Standard baseline risk of liver fat accumulation from diet alone. |
| CG (Carrier) | Moderate | One copy of the risk allele (CG). Moderately reduced enzyme activity; diet quality has a noticeably higher impact on liver fat accumulation. |
| GG (Variant) | High impact | Two copies of the risk allele (GG). Substantially reduced triglyceride breakdown in the liver, meaningfully raising NAFLD risk, especially with high-calorie, high-fat, or high-fructose diets. Fermented vegetables such as kimchi have been associated with reduced risk in carriers of this genotype. |
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