Recently, the PNPLA3 gene rs738409" genes_norm="80339">I148M (rs738409) variant was demonstrated to be strongly associated with hepatic steatosis in obese adults.
In a case only analysis of G allele of rs738409 in PNPLA3 was associated with a decreased risk of zone 3 centered steatosis (OR = 0.46, 95% CI = 0.36-0.58; P = 5.15 x 10(-11)).
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)).
A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance.
In multivariate logistic regression, the relationship between the highest quartile of CIMT and steatosis was different according to adiponutrin polymorphism.
NAFLD predisposition runs strongly in families and an allele in the PNPLA3 gene has shown a strong association with liver steatosis and hepatic inflammation.
Frequencies of allele PNPLA3rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03).
The rs738409PNPLA3 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 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.
We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner.
Although African Americans are less susceptible to fatty liver than European Americans, PNPLA3 appears to be a risk locus for hepatic steatosis in diabetic African Americans.
An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (rs738409" genes_norm="80339">p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis.
Before 2008, candidate gene studies based on prior knowledge of pathophysiology of fatty liver yielded conflicting results.In 2008, Romeo et al. published the first genome wide association study and reported the strongest genetic signal for the presence of fatty liver (PNPLA3, patatin-like phospholipase domain containing 3; rs738409).
Regarding the latter, a sequence variation within the gene coding for patatin-like phospholipase encoding 3 (PNPLA3, rs738409) was found to modulate steatosis, necroinflammation and fibrosis in NAFLD.
PNPLA3 p.148M/M genotype was negatively associated with SVR and early viral kinetics independently of steatosis, albeit only in difficult-to-cure G1/4 patients with advanced fibrosis, whereas stratification for the p.148M/M PNPLA3 genotype unmasked an association between IL28B CC genotype and more severe liver fibrosis.
IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis.
A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children.