This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases.
Our findings indicated that the <i>PNPLA3</i> rs738409 polymorphism may serve as a potential biological marker of hepatocellular carcinoma in Caucasians.
Expandable primary human (upcyte®) hepatocytes and human PLC/PRF/5 hepatoma cells were lentivirally transduced with both PNPLA3 I148M variants and stimulated with lipids.
Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown.
Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.
Variation at rs738409 was not associated with significant changes in resolution rate of hepatitis C. By contrast, M/M genotype, present at higher frequencies (22.8%) in HCC patients than in patients with chronic hepatitis C (8.5%, P = 0.004) or control individuals (9.1%, P = 0.005) was associated with a 3-fold increase of liver cancer risk.
Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies.
The current study is the first prospective report showing the association of the PNPLA3 I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
In particular, the common I148M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis.
Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited.
Carriage of the PNPLA3 rs738409 C >G polymorphism is not only associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC.
In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients.
G allele of PNPLA3 rs738409 variant was significantly higher in NBNC-HCC (49%) compared to healthy controls (32%), HBV-HCC (32%) and HCV-HCC (31%) (P < 0.001).
Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95% CI 0.72-0.88], p=8.13×10-6) and HCC (OR 0.77 [95% CI 0.68-0.89], p=2.27×10-4), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95% CI 1.54-1.88], p=1.52x10-26) and HCC (OR 1.77 [95% CI 1.58-1.98], p=2.31×10-23).