Research
Mixed
Genetic variants, specifically PNPLA3 I148M and TM6SF2 E167K, significantly increase the risk of liver disease progression and hepatocellular carcinoma in NAFLD patients, independent of metabolic syndrome severity.
If you have a family history of liver disease or known genetic variants like PNPLA3, you are at higher risk for liver damage even if your weight is normal. This means you need stricter monitoring of liver enzymes and fibrosis markers, and you must be aggressive with lifestyle interventions to reduce liver fat and inflammation.
GoodSupportsHIGH confidence
The nonsynonymous variant rs738409 of PNPLA3 is a genetic polymorphism characterized by the substitution of isoleucine to methionine at position 148 (I148M). Studies consistently show a strong association between I148M variant and hepatocellular triglycerides accumulation
Why this rating
Supported by multiple genetic association studies and meta-analyses cited in the review.
Source
Nonalcoholic fatty liver disease: Evolving paradigms
Amedeo Lonardo et al. · World Journal of Gastroenterology · 2017
DOI 10.3748/wjg.v23.i36.6571
narrative_reviewCited 199×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Nonalcoholic fatty liver disease (NAFLD) is a systemic condition with multifactorial pathogenesis, not merely a hepatic manifestation of metabolic syndrome, and it can precede the development of metabolic syndrome and type 2 diabetes.Good
- Lean NAFLD is a distinct phenotype characterized by visceral adiposity and metabolic abnormalities despite normal BMI, and it carries similar cardio-metabolic risks to obese NAFLD.Good
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