Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection.
Furthermore, the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis, and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly chronic hepatitis B virus hepatitis, hereditary hemochromatosis and primary sclerosing cholangitis.
Three SNP-diagnosis pairs passed the phenome-wide significance threshold: rs9273349 and E06 (thyroiditis, p = 5.50x10-8); rs9273349 and E10 (type-1 diabetes, p = 2.60x10-7); and rs2281135 and K76 (non-alcoholic liver diseases, including NAFLD, p = 4.10x10-7).
IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10(-7); rs2896019, p = 7.56 × 10(-4)); clinically significant steatosis (rs12979860, p = 1.82 × 10(-3); rs2896019, p = 1.27 × 10(-4)); and steatosis severity (rs12979860, p = 2.05 × 10(-8); rs2896019, p = 2.62 × 10(-6)).
Previous studies of the PNPLA3 I148M</span> sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis.
The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models.
In patients with NAFLD, adiponutrin rs738409 C-->G genotype, encoding for I148M, is associated with the severity of steatosis and fibrosis and the presence of nonalcoholic steatohepatitis.
The PNPLA3 rs738409 variant influences histological liver damage in Japanese patients with chronic hepatitis C. The G allele homozygotes are at higher risk for hepatic steatosis, severe necroinflammation, and advanced fibrosis.
The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis.
A genetic variant in adiponutrin (PNPLA3) gene, rs738409 C/G, is associated with steatosis, severity, and progression of liver fibrosis in CHC patients, and predicts treatment outcome in difficult-to-cure HCV-infected patients with advanced fibrosis.
The presence of the minor PNPLA3 p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P < 0.05).
The influence of recipient and donor TM6SF2 genotypes, PNPLA3 rs738409 genotypes and nongenetic factors on the steatosis grade assessed 6 - 30 months after transplantation was analyzed by ordinal logistic regression.
The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented.
The PNPLA3 rs738409 GG genotype is positively associated with HS, while the IFNL3 rs 12979860 CC genotype may be negatively associated with HS, in Asian CHC patients.