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Association of the tumor necrosis factor ‐308 A / G promoter polymorphism with T ourette syndrome
Author(s) -
Keszler G.,
Kruk E.,
Kenezloi E.,
Tarnok Z.,
SasvariSzekely M.,
Nemoda Z.
Publication year - 2014
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12147
Subject(s) - allele , transmission disequilibrium test , genotype , tumor necrosis factor alpha , immunology , medicine , single nucleotide polymorphism , biology , genetics , gene
Summary 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 T ourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.