title: Association of the tumor necrosis factor -308 A/G promoter polymorphism with Tourette syndrome.
abstract: Several lines of evidence suggest that certain subtypes of obsessive-compulsive and tic disorders might be paediatric manifestations of post-streptococcal autoimmunity caused by cross-reactive autoantibodies. As tumor necrosis factor (TNF) is known to play a seminal role in coordinating the humoral immune response, TNF gene polymorphisms have been proposed as genetic risk factors both in obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). The aim of this study was to investigate two TNF promoter polymorphisms (-238 A/G: rs361525 and -308 A/G: rs1800629) on the genetic susceptibility to OCD and TS in a child psychiatric sample (102 patients with OCD and 117 patients with TS). In the case-control set-up, the genotype and allele frequencies were compared to a control group from the general population (n = 405). As a control child psychiatric sample, 194 children with attention-deficit hyperactivity disorder were also genotyped. Our results revealed that the TNF -308 G-allele was more frequent in children with TS compared to controls (90.2% vs 84.8%, P = 0.037). For confirmation of this genetic association, a family-based analysis, the transmission disequilibrium test was used, which showed preferential transmission of the G-allele to patients with TS (nominal P-value 0.011). Moreover, this allele was also transmitted more frequently to children with tic symptoms (nominal P-value 0.039). No association was found between OCD or obsessive-compulsive symptoms and the studied TNF polymorphisms. Based on these findings, the TNF -308 G-allele can be associated with Tourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Keszler
authors.forename: E
authors.initials: E
authors.lastname: Kruk
authors.forename: E
authors.initials: E
authors.lastname: Kenezloi
authors.forename: Z
authors.initials: Z
authors.lastname: Tarnok
authors.forename: M
authors.initials: M
authors.lastname: Sasvari-Szekely
authors.forename: Z
authors.initials: Z
authors.lastname: Nemoda
mesh_terms: D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D005879:Tourette Syndrome / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha