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From SNPedia

Geno Mag Summary
(C;C) 3.1 higher odds of alcoholic liver disease, increased liver fat
(C;G) 2 increased liver fat, odds of alcoholic liver disease
(G;G) 2.1 most common genotype; slightly less damage from alcohol
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs738409
1000 genomesrs738409
GWAS Ctlgrs738409
Max Magnitude3.1
? (C;C) (C;G) (G;G) 28

rs738409 is a SNP in the PNPLA3 gene. In all HapMap populations the most common allele is a C on the plus strand (coding for 148I), which means a G on the minus strand as represented for this SNP in dbSNP and in SNPedia. In the scientific literature, however, most authors appear unaware that this SNP is defined as oriented on the minus strand, so they refer incorrectly to rs738409(G) as the minor allele. The genotypes defined in SNPedia are correct for the minus orientation of this SNP, but this can be confusing since it's the opposite of what the literature indicates in many cases.

[PMID 19946271] In a Mestizo population, rs738409 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis (unadjusted odds ratio 2.25, p=1.7e-10); ancestry-adjusted OR 1.79, p=1.9 x 10(-5)).

[PMID 19224197] rs738409(G) increased quantitative measures of liver fat content


Nonalcoholic fatty liver disease.

Fat content 2x for rs738409(G;G)

rs738409(G) (I148M) was strongly associated with increased hepatic fat levels (P = 5.9 times 10-10)


[PMID 19651814OA-icon.png] Dissociation between Fatty Liver and Insulin Resistance in Humans carrying a Variant of the Patatin-like Phospholipase 3 Gene

[PMID 19729411OA-icon.png] Genetic Evidence for a Role of Adiponutrin in the Metabolism of Apolipoprotein B-Containing Lipoproteins

[PMID 19738004OA-icon.png] A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity

[PMID 19844213] Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent

[PMID 20373368] Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease

[PMID 20684021OA-icon.png] The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease

[PMID 20826584] Specifically PNPLA3-Mediated Accumulation of Liver Fat in Obese Patients with Type 2 Diabetes

[PMID 20585554OA-icon.png] 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

[PMID 21140471] Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

[PMID 21176169OA-icon.png] Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease

[PMID 21236304] Viral Genotype-Specific Role of PNPLA3, PPARG, MTTP and IL28B in Hepatitis C Virus-Associated Steatosis

[PMID 21281435OA-icon.png] Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study


[PMID 21488075] Impact of PNPLA3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C

GWAS snp
PMID [PMID 21423719OA-icon.png]
Title Genome-wide association analysis identifies variants associated with nonalcoholic Fatty liver disease that have distinct effects on metabolic traits
Risk Allele G
P-val 4E-34
Odds Ratio 0.2600 [0.22-0.30] unit increase (GOLD)

[PMID 21525193] Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans

[PMID 21665509OA-icon.png] Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus

[PMID 22087248OA-icon.png] 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

[PMID 22105854OA-icon.png] A variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents

[PMID 22110053] Genetic determinants of alcoholic liver disease

[PMID 22141340] Genetic variation in PNPLA3 but not APOC3 influences liver fat in NAFLD

GWAS snp
PMID [PMID 22001757OA-icon.png]
Title Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
Risk Allele G
P-val 1E-45
Odds Ratio 6.0000 None

[PMID 22276112OA-icon.png] A Common Variant of PNPLA3 (p.I148M) Is Not Associated with Alcoholic Chronic Pancreatitis

[PMID 22634340] Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C

[PMID 22629460OA-icon.png] Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake

[PMID 22719190OA-icon.png] Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis

[PMID 22724004OA-icon.png] Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant

[PMID 22792295OA-icon.png] The PNPLA3 rs738409 G-Allele Associates with Reduced Fasting Serum Triglyceride and Serum Cholesterol in Danes with Impaired Glucose Regulation

[PMID 18728122] Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity.

[PMID 18940312OA-icon.png] Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.

[PMID 19524579] Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors.

[PMID 19542081OA-icon.png] A common variant in the adiponutrin gene influences liver enzyme values.

[PMID 20546964] The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life.

[PMID 20648472OA-icon.png] PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease.

[PMID 20648474] I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease.

[PMID 20648554OA-icon.png] Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease.

[PMID 20803499OA-icon.png] A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents.

[PMID 20852027OA-icon.png] Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents.

[PMID 20962157OA-icon.png] Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption.

[PMID 21068004OA-icon.png] Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome.

[PMID 21168155] A common variant in the PNPLA3 gene is a risk factor for non-alcoholic fatty liver disease in obese Taiwanese children.

[PMID 21168459] Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease.

[PMID 21254164] Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians.

[PMID 21274868OA-icon.png] Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance.

[PMID 21319195] Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C.

[PMID 21334404] Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease.

[PMID 21339799OA-icon.png] Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

[PMID 21381068] 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.

[PMID 22162034] PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis.

[PMID 22314430] IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease.

[PMID 22338072] PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis.

[PMID 22546774OA-icon.png] PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: The NHLBI Family Heart Study.

GWAS snp
PMID [PMID 22719876OA-icon.png]
Title Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese.
Risk Allele G
P-val 1E-10
Odds Ratio 1.6600 None

[PMID 23155331OA-icon.png] PNPLA3, the triacylglycerol synthesis/hydrolysis/storage dilemma, and nonalcoholic fatty liver disease

[PMID 23269818] A common variant in the peroxisome proliferator-activated receptor-γ coactivator-1α gene is associated with nonalcoholic fatty liver disease in obese children

[PMID 23418085OA-icon.png] Interactions of allelic variance of PNPLA3 with non genetic factors in predicting NASH and non-hepatic complications of severe obesity

[PMID 23484035OA-icon.png] Susceptibility and Gene Interaction Study of the Angiotensin II Type 1 Receptor (AGTR1) Gene Polymorphisms with Non-Alcoholic Fatty Liver Disease in a Multi-Ethnic Population

[PMID 23512881] A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population

[PMID 23734760] Genetic Variation in the Patatin-Like Phospholipase Domain-Containing Protein-3 (PNPLA-3) Gene in Asian Indians with Nonalcoholic Fatty Liver Disease

[PMID 24102786OA-icon.png] PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis

[PMID 24114809] Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: evidence from a meta-analysis of individual participant data

[PMID 24125181] The Impact of PNPLA3 Polymorphisms on the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Virus Infection

[PMID 24425067] Response to the letter of Limagne et al. PNPLA3 (rs738409 C>G) variant and oxidative stress due to chronic liver damage

[PMID 24477042] Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals

[PMID 24553484] Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor

[PMID 22258181OA-icon.png] A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease.

[PMID 22704398] PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals.

[PMID 22863264] Genetic polymorphism in cyclooxygenase-2 promoter affects hepatic inflammation and fibrosis in patients with chronic hepatitis C.

[PMID 22863562OA-icon.png] PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American population.

[PMID 22869157] The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis.

[PMID 22878467] Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro.

[PMID 22884299] PNPLA3, a genetic marker of progressive liver disease, still hiding its metabolic function?

[PMID 23032985OA-icon.png] The interaction of rs738409, obesity, and alcohol: a population-based autopsy study.

[PMID 23069476] PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis.

[PMID 23275357OA-icon.png] The association between hepatic fat content and liver injury in obese children and adolescents: effects of ethnicity, insulin resistance, and common gene variants.

[PMID 23292069OA-icon.png] Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis.

[PMID 23334462] Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3.

[PMID 23535911] 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.

[PMID 23564580] Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B.

[PMID 23776098OA-icon.png] Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.

[PMID 23800943] Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene.

[PMID 23815500OA-icon.png] Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents?

[PMID 24799990OA-icon.png] Pediatric non-alcoholic fatty liver disease: New insights and future directions

[PMID 24831885] Genetic Variants in the PNPLA3 Gene Are Associated with Nonalcoholic Steatohepatitis

[PMID 24917523OA-icon.png] Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis

[PMID 24916969] Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study

[PMID 23872669] Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis

[PMID 25069572] Role of the PNPLA3 I148M Polymorphism in Nonalcoholic Fatty Liver Disease and Fibrosis in Korea

[PMID 25074358] Association between genetic variants in PNPLA3 and serum adiponectin

[PMID 25232397OA-icon.png] Genetic variation I148M in patatin-like phospholipase 3 gene and risk of non-alcoholic fatty liver disease among Filipinos

[PMID 24349054OA-icon.png] No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV

[PMID 25457210] Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection

[PMID 25641744] PNPLA3 Polymorphisms (rs738409) and Non-Alcoholic Fatty Liver Disease Risk and Related Phenotypes: A Meta-Analysis

[PMID 25646328] Isoleucine-to-methionine substitution at residue 148 variant of PNPLA3 gene and metabolic outcomes in gestational diabetes

[PMID 25678388] Hepatic steatosis in Wilson disease - role of copper and PNPLA3 mutations

[PMID 25676803] The 148M allele of the PNPLA3 gene is associated with plasma irisin levels in a population sample of Caucasian children: The PANIC Study

[PMID 25713769OA-icon.png] PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients

[PMID 25791171OA-icon.png] Association Between Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) Polymorphisms and Nonalcoholic Fatty Liver Disease: A HuGE Review and Meta-Analysis

[PMID 25801076] PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C

[PMID 26147768] Influence of the rs738409 polymorphism in PNPLA3 on the treatment efficacy of nonalcoholic fatty liver disease with type 2 diabetes mellitus

[PMID 26200108OA-icon.png] Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

[PMID 26305067] A Variant in PNPLA3 Associated with Fibrosis Progression but not Hepatocellular Carcinoma in Patients With HCV Infection

[PMID 26337813] The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus

[PMID 26389885OA-icon.png] Duplex High-Resolution Melting Assay for the Simultaneous Genotyping of IL28B rs12979860 and PNPLA3 rs738409 Polymorphisms in Chronic Hepatitis C Patients

[PMID 26457389OA-icon.png] Role of the TM6SF2 rs58542926 in the pathogenesis of non-alcoholic pediatric fatty liver disease (NAFLD): A multiethnic study

[PMID 26493626] PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis

[PMID 23870067] Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C

[PMID 26599080OA-icon.png] The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection

[PMID 26847197OA-icon.png] Association of PNPLA3 rs738409 and TM6SF2 rs58542926 with health services utilization in a population-based study.

[PMID 27150500] The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients.

[PMID 27744419OA-icon.png] Transcriptional regulation of PNPLA3 and its impact on susceptibility to nonalcoholic fatty liver Disease (NAFLD) in humans.

[PMID 26745088] Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases.

[PMID 28338112] PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population.

Risk Rs738409(C;C)
Alt Rs738409(C;C)
Reference Rs738409(G;G)
Significance Probable-non-pathogenic
Disease Susceptibility to Nonalcoholic Fatty Liver Disease
Variation info
CLNDBN Susceptibility to Nonalcoholic Fatty Liver Disease
Reversed 1
HGVS NC_000022.10:g.44324727C>G
CLNACC RCV000299548.1,

[PMID 29055919] The Expression of PNPLA3 Polymorphism could be the Key for Severe Liver Disease in NAFLD in Hispanic Population.

[PMID 29218813] Association of PNPLA3 rs738409 polymorphism with Liver Steatosis but not with Cirrhosis in Patients with HBV Infection: Systematic Review with Meta-analysis.

[PMID 29242078] Response to: The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort.

[PMID 29474507OA-icon.png] PNPLA3 Association with Alcoholic Liver Disease in a Cohort of Heavy Drinkers.

[PMID 29578593OA-icon.png] High frequency of the PNPLA3 rs738409 [G] single-nucleotide polymorphism in Hmong individuals as a potential basis for a predisposition to chronic liver disease.

[PMID 30027138OA-icon.png] Patatin-like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events.

[PMID 30176114] Relationship between nonalcoholic steatohepatitis, PNPLA3 I148M genotype and bone mineral density in adolescents.

[PMID 30289982] PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases.

[PMID 30444569] Genetic determinants of steatosis and fibrosis progression in pediatric non-alcoholic fatty liver disease.

[PMID 30487694OA-icon.png] Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables.

[PMID 30564000OA-icon.png] Genetic and Epigenetic Culprits in the Pathogenesis of Nonalcoholic Fatty Liver Disease.

[PMID 30572387] [Effects of PNPLA3, TM6SF2 gene polymorphisms and its interactions with smoking and alcohol drinking on hepatitis B virus-associated hepatocellular carcinoma].

[PMID 30875804OA-icon.png] TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis.

[PMID 30912854] Relationship between PNPLA3 rs738409 polymorphism and decreased kidney function in children with NAFLD.

[PMID 31311600OA-icon.png] GWAS and enrichment analyses of non-alcoholic fatty liver disease identify new trait-associated genes and pathways across eMERGE Network.

[PMID 31826071] Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

[PMID 32062042] Development and Validation of a Scoring System, Based on Genetic and Clinical Factors, to Determine Risk of Steatohepatitis in Asian Patients with Nonalcoholic Fatty Liver Disease.

[PMID 32256016OA-icon.png] Importance of genetic polymorphisms in liver transplantation outcomes.

[PMID 32298765] Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically-characterised cohort.

[PMID 32342668] Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non-alcoholic fatty liver disease.

[PMID 32349377OA-icon.png] Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

[PMID 32871288] PNPLA3 rs738409 associates with alcoholic liver cirrhosis but not with serum levels of IL6, IL10, IL8 or CCL2 in the Russian population.

[PMID 32910776] Role of Patatin-Like Phospholipase Domain-Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes.

[PMID 33036387OA-icon.png] Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings.

[PMID 33476381] Study of CXCL9-11 gene polymorphisms in liver fibrosis among patients with chronic hepatitis C.