title: The adiponutrin I148M variant is a risk factor for HCV-associated liver cancer in North-African patients.
abstract: Recent reports revealed an association between variation in the PNPLA3 gene and alcohol-induced hepatocellular carcinoma among Europeans. We have assessed whether the PNPLA3 rs738409 (I148M) polymorphism may also affect the resolution and/or the progression of hepatitis C in a Moroccan cohort. Genotype and allele frequencies at rs738409 were determined using a TaqMan 5' allelic discrimination assay in 437 individuals. Among them, 230 patients had a persistent infection with hepatitis C virus (HCV) with 129 patients affected by a chronic hepatitis and 101 patients by a hepatocellular carcinoma (HCC). In addition, we analyzed 75 individuals who naturally cleared HCV and 132 healthy subjects. 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. In North African subjects, the PNPLA3 I148M variant apparently stimulates liver cancer development without interfering on the HCV clearance process. This polymorphism may, therefore, represent a valuable genetic marker to monitor liver cancer risk in populations from the Southern bank of the Mediterranean.
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco. Electronic address: sayeh.ezzikouri@pasteur.ma.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Ezzikouri
authors.affiliation: Service de Médecine B, CHU Ibn Rochd, Casablanca, Morocco.
authors.forename: Rhimou
authors.initials: R
authors.lastname: Alaoui
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Sana
authors.initials: S
authors.lastname: Tazi
authors.affiliation: Service de Médecine B, CHU Ibn Rochd, Casablanca, Morocco.
authors.forename: Salwa
authors.initials: S
authors.lastname: Nadir
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Naima
authors.initials: N
authors.lastname: Elmdaghri
authors.affiliation: Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.affiliation: Virology Unit, Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015613:Hepadnaviridae / Q000502:physiology*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications* / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Genetic marker; Hepatocellular carcinoma; PNPLA3; Spontaneous clearance