The impact of polymorphism in PNPLA3 and TM6SF2 genes on the susceptibility and survival of hepatitis C-related Hepatocellular carcinoma

Abstract Background: Genetic variants of Patatin-like phospholipase domain-containing protein3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have beenreported with development of hepatocellular carcinoma (HCC). Aim: To explore therole of The PNPLA3 rs738409 and TM6SF2 rs58542926 single nucleotidepolymorphisms (SNPs) on the incidence and survival of HCV induced HCC inEgyptians.Method: This case-control study included (120) HCC and (144) HepatitisC virus (HCV) patients. Baseline clinical, laboratory, tumor characteristics data, HCCrecurrence, and overall survival were collected. PNPLA3 rs738409 and TM6SF2rs58542926 polymorphism were detected by TaqMan allelic discrimination assay.Results: HCC Patients were significantly older with male predominance. A significantdifference between TT genotype of TM6SF2 frequency was observed in HCCcompared with HCV patients. Moreover, T allele of TM6SF2 distributions revealedsignificant contribution with different stages of HCC ( p =0.03). Both PNPLA3rs738409 and TM6SF2 rs58542926 variants showed significant relation with treatmentresponse according to the modified RECIST criteria. Age and diabetes mellitus werethe independent factors associated with the development of HCC by multivariateregression analysis. Diabetes, BCLC stage, performance status and response totreatment were significantly associated with patients’ survival.Conclusion : TM6SF2 rs58542926 polymorphism not PNPLA3 rs738409 could be implicated in thedevelopment HCV induced HCC and its progression.