title: Association of ADORA1 rs2228079 and ADORA2A rs5751876 Polymorphisms with Gilles de la Tourette Syndrome in the Polish Population.
abstract: BACKGROUND
  Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics. Hyperactivity of dopaminergic transmission is considered a prime abnormality in the pathophysiology of tics. There are reciprocal antagonistic interactions between adenosine and dopamine transmission. The aim of the study was to analyze the association of two polymorphisms, rs2228079 in ADORA1 and rs5751876 in ADORA2A, with the risk of GTS and co-morbid disorders.
  
  
  METHODS
  A total of 162 Polish GTS patients and 270 healthy persons were enrolled in the study. Two polymorphisms were selected on the basis of knowledge of SNPs frequencies in ADORA1 and ADORA2A. Chi-square test was used for allelic and genotypic association studies. Association of genotypes with age of tic onset was analyzed with Mann-Whitney test. Multivariate logistic regression was used to find independent predictors of GTS risk.
  
  
  RESULTS
  We found that the risk of GTS was associated with rs2228079 and rs5751876 polymorphisms. The GG+GT genotypes of rs2228079 in ADORA1 were underrepresented in GTS patients (p = 0.011), whereas T allele of rs5751876 in ADORA2A was overrepresented (p = 0.017). The GG genotype of rs2228079 was associated with earlier age of tic onset (p = 0.046). We found also that the minor allele G of rs2228079 was more frequent in GTS patients with depression as compared to the patients without depression (p = 0.015). Also the genotype GG was significantly more frequent in patients with obsessive compulsive disorder/behavior (OCD/OCB, p = 0.021) and depression (p = 0.032), as compared to the patients without these co-morbidities. The minor allele T frequency of rs5751876 was lower in GTS patients with co-morbid attention deficit hyperactivity disorder (p = 0.022), and TT+TC genotypes were less frequent in the non-OCD anxiety disorder group (p = 0.045).
  
  
  CONCLUSIONS
  ADORA1 and ADORA2A variants are associated with the risk of GTS, co-morbid disorders, and may affect the age of tic onset.
authors: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors: Piotr
authors: P
authors: Janik
authors: Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: Mariusz
authors: M
authors: Berdyński
authors: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors: Krzysztof
authors: K
authors: Safranow
authors: Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: Cezary
authors: C
authors: Żekanowski
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D005879:Tourette Syndrome / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C065666:purinoceptor RDC7; C065665:purinoceptor RDC8