PNPLA3

Summary

Gene Symbol: PNPLA3
Description: patatin like phospholipase domain containing 3
Alias: ADPN, C22orf20, iPLA(2)epsilon, patatin-like phospholipase domain-containing protein 3, acylglycerol O-acyltransferase, adiponutrin, calcium-independent phospholipase A2-epsilon, iPLA2-epsilon, iPLA2epsilon
Species: human
Products:     PNPLA3

Top Publications

  1. Dongiovanni P, Donati B, Fares R, Lombardi R, Mancina R, Romeo S, et al. PNPLA3 I148M polymorphism and progressive liver disease. World J Gastroenterol. 2013;19:6969-78 pubmed publisher
    The 148 Isoleucine to Methionine protein variant (I148M) of patatin-like phospholipase domain-containing 3 (PNPLA3), a protein is expressed in the liver and is involved in lipid metabolism, has recently been identified as a major ..
  2. Romeo S, Sentinelli F, Dash S, Yeo G, Savage D, Leonetti F, et al. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. Int J Obes (Lond). 2010;34:190-4 pubmed publisher
    The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic steatosis...
  3. Liu Y, Moldes M, Bastard J, Bruckert E, Viguerie N, Hainque B, et al. Adiponutrin: A new gene regulated by energy balance in human adipose tissue. J Clin Endocrinol Metab. 2004;89:2684-9 pubmed
    b>Adiponutrin is a newly identified nonsecreted adipocyte protein regulated by changes in energy balance in rodents. We documented the influence of energy balance modification on adiponutrin gene expression in humans...
  4. Sookoian S, Castano G, Burgueño A, Gianotti T, Rosselli M, Pirola C. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res. 2009;50:2111-6 pubmed publisher
    We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of ..
  5. Zain S, Mohamed R, Mahadeva S, Cheah P, Rampal S, Basu R, et al. A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Hum Genet. 2012;131:1145-52 pubmed publisher
    The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts...
  6. Valenti L, Rumi M, Galmozzi E, Aghemo A, Del Menico B, De Nicola S, et al. Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology. 2011;53:791-9 pubmed publisher
    ..The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without ..
  7. Verrijken A, Beckers S, Francque S, Hilden H, Caron S, Zegers D, et al. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring). 2013;21:2138-45 pubmed publisher
    ..We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients...
  8. Calvo R, Obregon M. Tri-iodothyronine upregulates adiponutrin mRNA expression in rat and human adipocytes. Mol Cell Endocrinol. 2009;311:39-46 pubmed publisher
    b>Adiponutrin (PNPLA3) is expressed in adipose tissue. Although its precise function is unknown, some data suggest a dual role in lipid homeostasis...
  9. Wagenknecht L, Palmer N, Bowden D, Rotter J, Norris J, Ziegler J, et al. Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study. Liver Int. 2011;31:412-6 pubmed publisher
    ..A genetic variant in PNPLA3 (rs738409) has been identified as a strong predictor of hepatic fat content...

More Information

Publications79

  1. Li Q, Qu H, Rentfro A, Grove M, Mirza S, Lu Y, et al. PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American population. Clin Invest Med. 2012;35:E237-45 pubmed
    This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk ..
  2. Pingitore P, Pirazzi C, Mancina R, Motta B, Indiveri C, Pujia A, et al. Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta. 2014;1841:574-80 pubmed publisher
    The patatin-like phospholipase domain containing 3 (PNPLA3, also called adiponutrin, ADPN) is a membrane-bound protein highly expressed in the liver...
  3. Pirazzi C, Adiels M, Burza M, Mancina R, Levin M, Ståhlman M, et al. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. J Hepatol. 2012;57:1276-82 pubmed publisher
    ..The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated...
  4. Petta S, Grimaudo S, Cammà C, Cabibi D, Di Marco V, Licata G, et al. IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease. J Hepatol. 2012;56:1356-62 pubmed publisher
    ..The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients...
  5. Johansson L, Lindblad U, Larsson C, Rastam L, Ridderstrale M. Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. Eur J Endocrinol. 2008;159:577-83 pubmed publisher
    The insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis...
  6. Falleti E, Fabris C, Cmet S, Cussigh A, Bitetto D, Fontanini E, et al. PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence. Liver Int. 2011;31:1137-43 pubmed publisher
    The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non-alcoholic fatty liver disease and with alcoholic liver disease...
  7. Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson L, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137:865-72 pubmed publisher
    ..clinical and laboratory data and to test whether knowledge of the recently discovered genetic variant in the PNPLA3 gene (rs738409) increases accuracy of the prediction...
  8. Davis J, Le K, Walker R, Vikman S, Spruijt Metz D, Weigensberg M, et al. Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption. Am J Clin Nutr. 2010;92:1522-7 pubmed publisher
    Recently, a genetic variant (rs738409; C?G) of the PNPLA3 gene was identified to be associated with increased hepatic fat deposition, and the effect was more pronounced in Hispanics...
  9. Sookoian S, Pirola C. 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. Hepatology. 2011;53:1883-94 pubmed publisher
    ..to estimate 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...
  10. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio L, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461-5 pubmed publisher
    ..An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels (P = 5...
  11. Wang C, Lin H, Shin S, Yu M, Lin Z, Dai C, et al. The PNPLA3 I148M polymorphism is associated with insulin resistance and nonalcoholic fatty liver disease in a normoglycaemic population. Liver Int. 2011;31:1326-31 pubmed publisher
    The adiponutrin/patatin-like phospholipase-3 (PNPLA3) I148M polymorphism has recently been found to contribute to differences in hepatic lipid content...
  12. Petit J, Guiu B, Masson D, Duvillard L, Jooste V, Buffier P, et al. Specifically PNPLA3-mediated accumulation of liver fat in obese patients with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:E430-6 pubmed publisher
    Recently, it has been shown in the general population that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC), independently of visceral adiposity and insulin resistance...
  13. Valenti L, Alisi A, Galmozzi E, Bartuli A, Del Menico B, Alterio A, et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology. 2010;52:1274-80 pubmed publisher
    ..Recently, the rs738409 C>G adiponutrin/patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism, which encodes the I148M protein variant ..
  14. Hyysalo J, Stojkovic I, Kotronen A, Hakkarainen A, Sevastianova K, Makkonen J, et al. Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2012;27:951-6 pubmed publisher
    ..rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) influencing liver fat...
  15. Krawczyk M, Gruenhage F, Mahler M, Tirziu S, Acalovschi M, Lammert F. The common adiponutrin variant p.I148M does not confer gallstone risk but affects fasting glucose and triglyceride levels. J Physiol Pharmacol. 2011;62:369-75 pubmed
    Recently the common adiponutrin (PNPLA3) polymorphism p.I148M has been identified as a genetic determinant of severe forms of non-alcoholic fatty liver disease and alcoholic liver disease...
  16. Nischalke H, Berger C, Luda C, Berg T, Müller T, Grunhage F, et al. The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis. PLoS ONE. 2011;6:e27087 pubmed publisher
    An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis...
  17. Trépo E, Pradat P, Potthoff A, Momozawa Y, Quertinmont E, Gustot T, et al. Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology. 2011;54:60-9 pubmed publisher
    ..A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis ..
  18. He S, McPhaul C, Li J, Garuti R, Kinch L, Grishin N, et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem. 2010;285:6706-15 pubmed publisher
    ..Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content ..
  19. Kantartzis K, Peter A, Machicao F, Machann J, Wagner S, Königsrainer I, et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes. 2009;58:2616-23 pubmed publisher
    ..scan, the rs738409 C>G single nucleotide polymorphism (SNP) in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat but not with insulin resistance estimated from fasting values...
  20. Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Nakamura T, et al. Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. Hum Genet. 2013;132:783-92 pubmed publisher
    ..Rs738409 in the PNPLA3 gene was most strongly associated with NAFLD after adjustment (P = 6.8 × 10(-14), OR = 2.05)...
  21. Cox A, Wing M, Carr J, Hightower R, Smith S, Xu J, et al. Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus. Diabetes Metab. 2011;37:452-5 pubmed publisher
    ..2 diabetes mellitus (T2DM), and has been associated with the single nucleotide polymorphism (SNP) rs738409 in the PNPLA3 gene...
  22. Valenti L, Maggioni P, Piperno A, Rametta R, Pelucchi S, Mariani R, et al. Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis. World J Gastroenterol. 2012;18:2813-20 pubmed publisher
    To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH)...
  23. Burza M, Pirazzi C, Maglio C, Sjöholm K, Mancina R, Svensson P, et al. PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals. Dig Liver Dis. 2012;44:1037-41 pubmed publisher
    ..Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with ..
  24. Romeo S, Sentinelli F, Cambuli V, Incani M, Congiu T, Matta V, et al. The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life. J Hepatol. 2010;53:335-8 pubmed publisher
    ..Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity in children. Recently, the PNPLA3 gene I148M (rs738409) variant was demonstrated to be strongly associated with hepatic steatosis in obese adults...
  25. Valenti L, Dongiovanni P, Ginanni Corradini S, Burza M, Romeo S. PNPLA3 I148M variant and hepatocellular carcinoma: a common genetic variant for a rare disease. Dig Liver Dis. 2013;45:619-24 pubmed publisher
    ..The rs738409 genetic variant in the patatin-like phospholipase domain-containing 3 (PNPLA3, adiponutrin) gene has been implicated as a genetic determinant of the entire spectrum of liver diseases, ranging from ..
  26. Liu Y, Patman G, Leathart J, Piguet A, Burt A, Dufour J, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75-81 pubmed publisher
    ..Carriage of the PNPLA3 rs738409 c.444C >G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD...
  27. Lee S, Byoun Y, Jeong S, Woo B, Jang E, Kim J, et al. Role of the PNPLA3 I148M polymorphism in nonalcoholic fatty liver disease and fibrosis in Korea. Dig Dis Sci. 2014;59:2967-74 pubmed publisher
    The role of the patatin-like phospholipase domain-containing 3 (PNPLA3) single-nucleotide polymorphism (SNP), rs738409, in the development and progression of nonalcoholic fatty liver disease (NAFLD) has not been studied in the Korean ..
  28. Giudice E, Grandone A, Cirillo G, Santoro N, Amato A, Brienza C, et al. The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat. PLoS ONE. 2011;6:e27933 pubmed publisher
    A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity...
  29. Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Foufelle F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes. J Hepatol. 2011;55:145-53 pubmed publisher
    The adiponutrin/PNPLA3 (patatin-like phospholipase domain-containing protein 3) variant I148M has recently emerged as an important marker of human fatty liver disease...
  30. Trépo E, Gustot T, Degré D, Lemmers A, Verset L, Demetter P, et al. Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease. J Hepatol. 2011;55:906-12 pubmed publisher
    A recent genome-wide association study identified genetic polymorphism (rs738409 C>G) in the PNPLA3/adiponutrin gene associated with liver steatosis...
  31. Tian C, Stokowski R, Kershenobich D, Ballinger D, Hinds D. Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet. 2010;42:21-3 pubmed publisher
    Two genome-wide association studies (GWAS) have described associations of variants in PNPLA3 with nonalcoholic fatty liver and plasma liver enzyme levels...
  32. Valenti L, Rametta R, Ruscica M, Dongiovanni P, Steffani L, Motta B, et al. The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterol. 2012;12:111 pubmed
    ..liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still ..
  33. Huang Y, Cohen J, Hobbs H. Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease. J Biol Chem. 2011;286:37085-93 pubmed publisher
    A genetic variant of PNPLA3 (patatin-like phospholipase domain-containing 3; PNPLA3-I148M), a serine protease of unknown function, is associated with accumulation of triacylglycerol (TAG) in the liver...
  34. Speliotes E, Yerges Armstrong L, Wu J, Hernaez R, Kim L, Palmer C, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7:e1001324 pubmed publisher
    ..liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis ..
  35. Cai T, Dufour J, Muellhaupt B, Gerlach T, Heim M, Moradpour D, et al. Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis. J Hepatol. 2011;55:529-535 pubmed publisher
    ..single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein (PNPLA3), were never evaluated...
  36. Lin Y, Chang P, Hu F, Yang W, Chang M, Ni Y. A common variant in the PNPLA3 gene is a risk factor for non-alcoholic fatty liver disease in obese Taiwanese children. J Pediatr. 2011;158:740-4 pubmed publisher
    To test the hypothesis that the presence of the PNPLA3 rs738409 G allele would increase the susceptibility of non-alcoholic fatty liver disease (NAFLD) in obese Taiwanese children...
  37. Perttilä J, Huaman Samanez C, Caron S, Tanhuanpää K, Staels B, Yki Jarvinen H, et al. PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis. Am J Physiol Endocrinol Metab. 2012;302:E1063-9 pubmed publisher
    ..G allele in rs738409 (I148M amino acid substitution) in patatin-like phospholipase domain-containing 3 (PNPLA3)/adiponutrin. We studied transcriptional regulation of PNPLA3 in immortalized human hepatocytes (IHH) and human hepatoma ..
  38. Kollerits B, Coassin S, Beckmann N, Teumer A, Kiechl S, Doring A, et al. Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. Hum Mol Genet. 2009;18:4669-76 pubmed publisher
    b>Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding...
  39. Rae Whitcombe S, Kennedy D, Voyles M, Thompson M. Regulation of the promoter region of the human adiponutrin/PNPLA3 gene by glucose and insulin. Biochem Biophys Res Commun. 2010;402:767-72 pubmed publisher
    The adiponutrin/PNPLA3 gene is highly expressed in adipose tissue and liver. Its expression is down-regulated by fasting and rapidly induced by refeeding a high carbohydrate diet...
  40. Kawaguchi T, Sumida Y, Umemura A, Matsuo K, Takahashi M, Takamura T, et al. Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. PLoS ONE. 2012;7:e38322 pubmed publisher
    ..A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409...
  41. Sevastianova K, Kotronen A, Gastaldelli A, Perttilä J, Hakkarainen A, Lundbom J, et al. Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans. Am J Clin Nutr. 2011;94:104-11 pubmed publisher
    The rs738409 C?G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance...
  42. Valenti L, Aghemo A, Stättermayer A, Maggioni P, De Nicola S, Motta B, et al. Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin. Aliment Pharmacol Ther. 2012;35:1434-42 pubmed publisher
    Homozygosity for the PNPLA3 p.I148M polymorphism influences steatosis and fibrogenesis in chronic hepatitis C (CHC). To evaluate the effect of p...
  43. Hotta K, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, et al. Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC Med Genet. 2010;11:172 pubmed publisher
    ..association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat content...
  44. Jenkins C, Mancuso D, Yan W, Sims H, Gibson B, Gross R. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem. 2004;279:48968-75 pubmed
    ..consensus sequence motifs identified a novel subfamily of three putative iPLA2/lipase family members designated iPLA2epsilon, iPLA2zeta, and iPLA2eta (previously named adiponutrin, TTS-2...
  45. Hyysalo J, Gopalacharyulu P, Bian H, Hyötyläinen T, Leivonen M, Jaser N, et al. Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity. Diabetes. 2014;63:312-22 pubmed publisher
    ..relative concentrations of circulating triacylglycerols (TAGs) between carriers compared with noncarriers of PNPLA3(I148M) gene variant display deficiency of TAGs, which accumulate in the liver because of defective lipase activity...
  46. Lake A, Sun Y, Li J, Kim J, Johnson J, Li D, et al. Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members. J Lipid Res. 2005;46:2477-87 pubmed
    b>Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity...
  47. Valenti L, Al Serri A, Daly A, Galmozzi E, Rametta R, Dongiovanni P, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51:1209-17 pubmed publisher
    ..predisposition to nonalcoholic fatty liver disease (NAFLD), and the rs738409 C-->G polymorphism of PNPLA3/adiponutrin, encoding for the isoleucine-to-methionine substitution at residue 148 (I148M) protein variant, has recently ..
  48. Sookoian S, Pirola C. PNPLA3, the triacylglycerol synthesis/hydrolysis/storage dilemma, and nonalcoholic fatty liver disease. World J Gastroenterol. 2012;18:6018-26 pubmed publisher
    ..susceptibility of NAFLD in humans is patatin-like phospholipase domain containing 3 (PNPLA3, also known as adiponutrin)...
  49. Petit J, Guiu B, Masson D, Duvillard L, Jooste V, Buffier P, et al. PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes. Liver Int. 2011;31:1332-6 pubmed publisher
    Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance...
  50. Speliotes E, Butler J, Palmer C, Voight B, Hirschhorn J. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology. 2010;52:904-12 pubmed publisher
    ..The G allele of rs738409 in PNPLA3 was associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.26, 95% confidence intervals [CI] = 2...
  51. Li Y, Xing C, Tian Z, Ku H. Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population. BMC Med Genet. 2012;13:113 pubmed publisher
    ..single nucleotide polymorphism rs738409 (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) predisposes susceptibility to NAFLD; however, its association with steatosis grade is inconsistent in the ..
  52. Palmer C, Maglio C, Pirazzi C, Burza M, Adiels M, Burch L, et al. Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant. PLoS ONE. 2012;7:e39362 pubmed publisher
    ..The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis...
  53. Santoro N, Zhang C, Zhao H, Pakstis A, Kim G, Kursawe R, et al. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology. 2012;55:781-9 pubmed publisher
    ..Moreover, because recently rs738409 in the PNPLA3 and rs2854116 in the APOC3 were associated with fatty liver, we explored how the GCKR SNP and these two variants ..
  54. Wilson P, Gardner S, Lambie N, Commans S, Crowther D. Characterization of the human patatin-like phospholipase family. J Lipid Res. 2006;47:1940-9 pubmed
    ..Given the observed conservation of the patatin fold and lipase motif in all human PNPLAs, a single nomenclature to describe the PNPLA family is proposed. ..
  55. Rotman Y, Koh C, Zmuda J, Kleiner D, Liang T. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology. 2010;52:894-903 pubmed publisher
    ..C/G, a nonsynonymous coding SNP in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene encoding an Ile148Met change, was associated with steatosis (P = 0.03), portal inflammation (P = 2...
  56. Kienesberger P, Oberer M, Lass A, Zechner R. Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions. J Lipid Res. 2009;50 Suppl:S63-8 pubmed publisher
    ..This review aims to summarize current knowledge of PNPLA proteins and to document their emerging importance in lipid and energy homeostasis. ..
  57. Stickel F, Buch S, Lau K, Meyer zu Schwabedissen H, Berg T, Ridinger M, et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology. 2011;53:86-95 pubmed publisher
    A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content...
  58. Valenti L, Nobili V, Al Serri A, Rametta R, Leathart J, Zappa M, et al. The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver. J Hepatol. 2011;55:1409-14 pubmed publisher
    ..Stratification for the I148M PNPLA3 mutation, associated with the susceptibility to NASH, did not alter the results...
  59. Krawczyk M, Portincasa P, Lammert F. PNPLA3-associated steatohepatitis: toward a gene-based classification of fatty liver disease. Semin Liver Dis. 2013;33:369-79 pubmed publisher
    ..Recently, the common variant p.I148M of the enzyme adiponutrin (PNPLA3) has emerged as a major genetic determinant of hepatic steatosis and nonalcoholic steatohepatitis as ..
  60. Yuan X, Waterworth D, Perry J, Lim N, Song K, Chambers J, et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008;83:520-8 pubmed publisher
    ..two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), ..
  61. Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez A, et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012;15:691-702 pubmed publisher
    Numerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis...
  62. Kotronen A, Johansson L, Johansson L, Roos C, Westerbacka J, Hamsten A, et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009;52:1056-60 pubmed publisher
    It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups...
  63. Peng X, Wu Y, Lin S, Lu Q, Hu Z, Lin X. Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population. PLoS ONE. 2012;7:e50256 pubmed publisher
    We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (PNPLA3) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population...
  64. Goran M, Walker R, Le K, Mahurkar S, Vikman S, Davis J, et al. Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents. Diabetes. 2010;59:3127-30 pubmed publisher
    A genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ?twofold higher liver fat...
  65. Pare G, Cook N, Ridker P, Chasman D. On the use of variance per genotype as a tool to identify quantitative trait interaction effects: a report from the Women's Genome Health Study. PLoS Genet. 2010;6:e1000981 pubmed publisher
    ..levels, between the ICAM1 SNP rs1799969 and smoking in the prediction of soluble ICAM-1 levels, and between the PNPLA3 SNP rs738409 and body mass index in the prediction of soluble ICAM-1 levels...
  66. Krawczyk M, Grunhage F, Zimmer V, Lammert F. Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease. J Hepatol. 2011;55:299-306 pubmed publisher
    Recent genome-wide association studies have identified the variant p.I148M of the adiponutrin gene PNPLA3 as a risk factor for developing severe forms of non-alcoholic and alcoholic liver diseases...
  67. Lin Y, Chang P, Chang M, Ni Y. Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals. Am J Clin Nutr. 2014;99:869-74 pubmed publisher
    A genome-wide association study identified variants in or near patatin-like phospholipase domain-containing-3 (PNPLA3), neurocan (NCAN), lysophospholipase-like 1 (LYPLAL1), glucokinase regulatory protein (GCKR), and protein phosphatase 1 ..
  68. Guichelaar M, Gawrieh S, Olivier M, Viker K, Krishnan A, Sanderson S, et al. Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. Obesity (Silver Spring). 2013;21:1935-41 pubmed publisher
    Allelic variation (rs738409C?G) in adiponutrin (patatin-like phospholipase domain-containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis...
  69. Santoro N, Kursawe R, D Adamo E, Dykas D, Zhang C, Bale A, et al. A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology. 2010;52:1281-90 pubmed publisher
    ..Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults...
  70. Johansson L, Hoffstedt J, Parikh H, Carlsson E, Wabitsch M, Bondeson A, et al. Variation in the adiponutrin gene influences its expression and associates with obesity. Diabetes. 2006;55:826-33 pubmed
    b>Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes...