Impact of PNPLA3 and IFNL3 polymorphisms on hepatic steatosis in Asian patients with chronic hepatitis C

Abstract

Background and aimsA recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS) in Caucasian patients with chronic hepatitis C (CHC). However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3) rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations. In this study, then, we investigated the association of PNPLA3 and IFNL3 polymorphisms with HS in Asian CHC patients.MethodsWe enrolled consecutive CHC patients who underwent liver biopsy prior to antiviral therapy. We excluded those patients with decompensated liver disease, any co-existing chronic liver disease, or HIV or HBV co-infection.Results1080 CHC patients were enrolled, and HS was found in 453 (41.9%) patients. The frequency distribution of the G allele was significantly associated with HS (P<0.001), and this conferred a higher risk to G allele homozygotes (OR: 2.06, 95% CI: 1.46–2.88, P <0.001) than to G allele carriers (OR: 1.98, 95% CI: 1.52–2.58, P<0.001). There was a borderline significant difference in the prevalence of HS in rs12979860 CC versus non-CC (40.8% versus 49.3%, P = 0.059). After adjustment for age, sex, body mass index, diabetes, and excessive alcohol intake, the rs738409 G allele homozygote carriers still carried a higher risk for HS (OR: 1.93, 95% CI: 1.35–2.77, P = 0.003).ConclusionThe 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.

Association of Adiponutrin/Patatin Like Phospholipase 3 (PNPLA3) I148M Gene Variant with Chronic Hepatitis C in Egyptian Children

“…Previous studies found that PNPLA3 I148M is the most widely replicated genetic variant associated with increased hepatic steatosis [17-20, [74][75][76], and it has been observed that the GG genotype in CHC patients is associated with the greatest risk [21,22,24,54,62,[77][78][79][80]. In this study, we found that the mean CAP values of CAP steatosis stages among patients with CG and GG genotypes were significantly higher compared to those with CC genotype.…”

“…Meanwhile, Pirazzi et al demonstrated that PNPLA3 is highly expressed in human HSCs suggesting a potential link between HSCs, retinoid metabolism, and PNPLA3 in determining the susceptibility to hepatic fibrosis [83]. Discordant results were shown by Huang et al who found that the frequency of the rs738409 G allele was not significantly higher in CHC patients with advanced fibrosis (F3-F4 stages) than in patients with less advanced stages (F0-F2 stages) [80]. However, this result may have been related to the IFNL3 gene polymorphism, which is another factor associated with the severity of liver disease in CHC as other studies have explained [79,82].…”

The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C

“…When analyzing PNPLA3 polymorphisms, we found no association with liver steatosis or fibrosis in our cohort, despite other compelling data in this direction [ 24 , 25 , 39 – 41 ]. Huang et al (2017), found no significant association with the degree of liver fibrosis in 1,080 Asians with HCV [ 27 ]. Other studies have also found diverging results [ 26 , 42 ].…”

“…Studies on chronic hepatitis C corroborate the relationship of this polymorphism with liver disease progression and steatosis [ 19 , 24 , 25 ]. However, other studies with a predominance of Asian populations have shown divergent results [ 26 , 27 ].…”

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study

“…The dawn of genome-wide association study (GWAS) approach highlighted the potential role of host genetic factors related to hepatic fat metabolism [including PNPLA3 (adiponutrin or patatin-like phospholipase domain-containing protein 3) and TM6SF2 (transmembrane 6 superfamily member 2) in CLP, mainly in nonalcoholic fatty liver disease (NAFLD) settings [5,6]. In this context, PNPLA3 rs738409 polymorphism has been found associated with liver fat content [7], as well as with clinical phenotypes of steatosis, steatohepatitis and liver fibrosis/cirrhosis in various hepatic etiologies of nonviral [mainly NAFLD and alcoholic liver disease (ALD)] [8,9] and viral (mainly CHC) [10,11] origins. Functionally, carriers of the G allele at the above-mentioned locus have a reduced enzymatic activity of adiponutrin, resulting in high levels of intracellular triglyceride [12], that may subsequently result in the higher predisposition to hepatic scarring and HCC [13].…”