PNPLA3, the history of an orphan gene of the potato tuber protein family that found an organ: The liver

  title={PNPLA3, the history of an orphan gene of the potato tuber protein family that found an organ: The liver},
  author={Silvia Sookoian and Carlos Jose Pirola},
T he patatin-like phospholipase domain containing 3 gene (PNPLA3) was an orphan gene looking for a disease until 2008 when the first genome-wide association study (GWAS) on nonalcoholic fatty liver disease (NAFLD) showed the association between the risk of liver fat accumulation and the nonsynonymous rs738409 C/G variant. Months later, the variant was significantly associated with NAFLD disease severity and alanine aminotransferase (ALT) levels, and the role of PNPLA3 as a modifier of the… 
Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system
Analysis of pleiotropic associations within variants associated with hematologic traits and nonalcoholic fatty liver disease revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance pathways.
The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus
PNPLA3 and JAZF1 were associated with non-HBV and non-HCV-related HCC development among Japanese patients with T2DM.
Risk Factors for Fatty Liver in the Multicenter AIDS Cohort Study
CT-defined fatty liver is common among men at risk for HIV infection and is associated with greater visceral adiposity, HOMA-IR, and PNPLA3 (rs738409) non-CC genotype, although treated HIV infection was associated with a lower prevalence, and prolonged exposure to dideoxynucleoside analogs isassociated with higher prevalence.
Genetic and Epigenetic Associations with NAFLD: Focus on Clinical Decision Making and Novel Concepts in Disease Pathogenesis
New findings about current genome-wide association studies on NAFLD are summarized and controversies on the application of genetic testing to predict disease severity are discussed and specifically the role of rs738409 in clinical decision making are discussed.
Non-alcoholic fatty liver disease and risk of cardiovascular disease.
The impact of PNPLA3 (rs738409 C>G) polymorphisms on liver histology and long‐term clinical outcome in chronic hepatitis B patients
  • W. BrouwerA. Meer H. Janssen
  • Biology, Medicine
    Liver international : official journal of the International Association for the Study of the Liver
  • 2015
We aimed to assess the association between the patatin‐like phospholipase domain‐containing‐3 (PNPLA3) I148M polymorphism, liver histology and long‐term outcome in chronic hepatitis B (CHB) patients.
Personalizing care for nonalcoholic fatty liver disease patients: what are the research priorities?
The current knowledge and recent insights on NAFLD pathogenesis and diagnosis are revised in the context of a personalized perspective with special focus on the following issues: noninvasive biomarkers for the evaluation of disease severity and progression, lifestyle-related patients' recommendations, risk prediction of disease by genetic testing and patient-oriented therapeutic intervention strategies.


Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians
Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.
Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: Risk and prognosis prediction
PNPLA3 genetic variation may determine individual susceptibility to HCC development and poor prognosis, and further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PN PLA3.
Patatin‐Like phospholipase domain‐containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C
The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other Steatosis‐related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.
A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
The data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.
Patatin‐like phospholipase domain‐containing 3 I148M affects liver steatosis in patients with chronic hepatitis B
In CHB patients, the PNPLA3 I148M polymorphism influences susceptibility to Steatosis and, in particular, when associated with severe overweight and alcohol intake, severe steatosis.
Meta‐analysis of the influence of I148M variant of patatin‐like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease
Examining the strength of the effect of the I148M (rs738409 C/G) patatin‐like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations provided unequivocal evidence of rs738 409 as a strong modifier of the natural history of NAFLD in different populations around the world.
Impact of patatin‐like phospholipase‐3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C
The PNPLA3 (rs738409 C>G) polymorphism may represent a valuable genetic predictor and a potential therapeutic target inCHC liver damage and response to antiviral therapy in CHC.
Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta‐analysis of individual participant data
The results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.
Variant in PNPLA3 is associated with alcoholic liver disease
Investigating the contributions of these variants to liver disease in Mestizo subjects with a history of alcohol dependence found that rs738409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis.