title: The relationship between TNF alpha gene polymorphisms (-238/-308), TNF RII VNTR (p75) and outcomes of hepatitis B virus infection in Tunisian population.
abstract: The present study was undertaken to investigate the association between Hepatitis B Virus (HBV) infection and polymorphisms of tumour necrosis factor alpha TNF-α -308 G>A, TNF-α -238 G>A and TNF RII VNTR (p75) gene promoter in a Tunisian population. Blood samples were collected from 100 Tunisian patients with HBV infection, 45 with Chronic Hepatitis (CH), 36 with Liver Cirrhosis (LC), 15 with Hepatocellular Carcinoma (HCC) and 200 healthy individuals of similar ethnicity. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the analysed polymorphisms was performed using Amplified Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR), Restriction Fragment Length Polymorphism (RFLP) and Variable Number Tandem Repeat PCR (PCR-VNTR). The variant homozygotes -308 GG were associated with 50% decreased risk of HBV chronic infection (GG vs AA+GA; p=0.010; OR=0.50; 95%CI=0.29-0.85). However, the carriers of minor allele -308 A have higher risk (1.5 times) to develop a chronic infection than other patients (p=0.027; OR=1.46; 95%CI=1.04-2.06). The minor allele of -238 polymorphism was positively associated with virus resistance and the development of chronic infection (p=0.043; OR=1.42; 95%CI =1.01 1.99). The distribution of -308, -238 and TNF RII VNTR (p75) among the three groups differed significantly. For HCC groups, there were statistically significant differences in allele distribution in -308, -238 respectively in which A allele remains a risk factor for HBV evolution to HCC (p=0.008 and p=0.026). Haplotype analysis revealed that TNF-α (-308A; -238A) was significantly associated to HBV chronic infection and moreover to disease aggravation to HCC stage. Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-α and TNF RII might be an important risk factor, which could explain the variable outcomes of HBV infection.
authors.affiliation: University de Tunis El Manar, Faculty des Sciences de Tunis, LR 206 Micro-organisms and Bio-molecules Actives, Tunisia. Electronic address: sghaiere.ikram@gmail.com.
authors.forename: Ikram
authors.initials: I
authors.lastname: Sghaier
authors.affiliation: University de Tunis El Manar, Faculty des Sciences de Tunis, LR 206 Micro-organisms and Bio-molecules Actives, Tunisia.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zidi
authors.affiliation: Charles Nicolle Hospital, Hepato-Gastroenterology Department, Tunis, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Mouelhi
authors.affiliation: Charles Nicolle Hospital, Hepato-Gastroenterology Department, Tunis, Tunisia.
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dabbech
authors.affiliation: Military Hospital of Tunis, Laboratory of Immunology, Tunis, Tunisia.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Ghazouani
authors.affiliation: Department of Virology, Amiens University Hospital, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brochot
authors.affiliation: Research Unit of Haematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.affiliation: University de Tunis El Manar, Faculty des Sciences de Tunis, LR 206 Micro-organisms and Bio-molecules Actives, Tunisia.
authors.forename: Besma
authors.initials: B
authors.lastname: Yacoubi-Loueslati
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014416:Tunisia
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Cirrhosis; Gene polymorphism; HCC; Hepatitis B Virus; TNF RII (p75); TNF-α