title: Association of the Met-196-Arg variation of human tumor necrosis factor receptor 2 (TNFR2) with paranoid schizophrenia.
abstract: Research has provided strong evidence for oligodendrocyte and myelin-related genes dysfunction in schizophrenia. Several studies have suggested abnormalities in the expression of myelin-related genes including tumor necrosis factor receptor 2 (TNFR2) involved in the neurodegeneration and remyelination. In order to further assess the role of TNFR2 in schizophrenia, we examined a functional bi-allelic polymorphism associated with an impaired NF-KB signaling and cell survival. In the present case/control study, 220 patients with schizophrenia and 176 healthy controls were genotyped by RFLP-PCR for the T/G polymorphism at the position 676 in exon 6 of the TNFR2 gene. We found a trend towards over-representation of TNFR2 676G in the patients compared to the controls (p=0.19 and 0.09 respectively). Interestingly, when we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, our findings indicated that the frequencies of the G/G genotype and the G allele were significantly higher in paranoid (p=0.014 and p=0.012 respectively) and adult-onset paranoid (p=0.004 and p=0.004 respectively) schizophrenia patient group compared to the controls. The potential association was confirmed by a logistic regression model only for development of the paranoid form of schizophrenia (p=0.022) indicating a substantially increased risk for paranoid schizophrenia with inheritance of the TNFR2(G) allele. In conclusion, this polymorphism in TNFR2 or a gene in proximity seems to be associated specifically with paranoid schizophrenia, at least in the Tunisian population. A replication of our findings in other and larger populations could be of particular importance to establish TNFR2 as one of the susceptibility genes of paranoid schizophrenia.
authors.affiliation: 05UR/09-11, Institut Supérieur de Biotechnologie de Monastir, Monastir, Tunisia.
authors.forename: Sihem
authors.initials: S
authors.lastname: Thabet
authors.forename: Mouna
authors.initials: M
authors.lastname: Ben Nejma
authors.forename: Ferid
authors.initials: F
authors.lastname: Zaafrane
authors.forename: Lotfi
authors.initials: L
authors.lastname: Gaha
authors.forename: Kamel
authors.initials: K
authors.lastname: Ben Salem
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Romdhane
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nour
authors.forename: Besma Bel Hadj
authors.initials: BB
authors.lastname: Jrad
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics* / Q000276:immunology; D012563:Schizophrenia, Paranoid / Q000235:genetics* / Q000276:immunology; D014416:Tunisia; D055815:Young Adult
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II