Our aims were to develop a method to accurately predict non-alcoholic fatty liver disease (NAFLD) and liver fat content based on routinely available 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.
Two recent genome-wide association studies identified the liver expressed transmembrane protein adiponutrin to be associated with liver related phenotypes such as non-alcoholic fatty liver disease and liver function enzymes.
Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits.
PNPLA3 expression in wild-type C57BL/6 and NAFLD-susceptible LDL receptor knockout (LDLR-/-) mice was determined using microarray and real-time PCR analysis.
In this study, we investigated the association between the rs738409PNPLA3 gene polymorphism and NAFLD in 149 consecutive children and adolescents (age = 6-13 years) with biopsy-proven NAFLD.
After adjustment for age, sex, diabetes, and alcohol consumption, the minor allele of rs738409 C/G, a nonsynonymous coding SNP in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene encoding an rs738409" genes_norm="80339">Ile148Met change, was associated with steatosis (P = 0.03), portal inflammation (P = 2.5 x 10(-4)), lobular inflammation (P = 0.005), Mallory-Denk bodies (P = 0.015), NAFLD activity score (NAS, P = 0.004), and fibrosis (P = 7.7 x 10(-6)).
Homozygosity for the patatin-like phospholipase-3/adiponutrinI148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease.
Two genome-wide association studies (GWAS) have described associations of variants in PNPLA3 with nonalcoholic fatty liver and plasma liver enzyme levels.
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.
A recent finding that a nonsynonymous polymorphism in the PNPLA3 gene predicts the extent of steatosis in NAFLD has been replicated in at least eight studies, with several studies also demonstrating an association with fibrosis.
Finally, PNPLA3 polymorphisms were initially described as predictors of nonalcoholic fatty liver disease, but have recently been associated with disease progression in HCV.
The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3I148M genotype in patients with nonalcoholic fatty liver.
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 in nonalcoholic fatty liver disease.
Furthermore, there was a dose effect of the PNPLA3I148M genotype, in that CG heterozygotes had a risk of NAFLD between CC and GG homozygotes [adjusted odds ratio (OR)=2.03, 95% confidence interval (CI)=1.23-3.375 for the GG genotype and adjusted OR=1.55, 95% CI=1.02-2.35 for the CG genotype].