title: Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms.
abstract: BACKGROUND
  Major depressive disorder (MDD) and bipolar disorder (BPD) have significant genetic predisposition. The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a susceptibility gene for both MDD and BPD. In the current study the genetic effects of rs2230912 (Gln460Arg) and rs1653625 (located in the 3' untranslated region of the P2RX7 gene) were explored in mood disorders.
  
  
  METHODS
  Genotype frequencies were established in 315 patients (195 with MDD and 120 with BPD diagnosis) and in 373 controls. Depression severity was assessed by the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and by the self-report Hospital Anxiety and Depression Scale (HADS).
  
  
  RESULTS
  In the case-control analysis we did not find any significant differences between genotype frequencies of either BPD or MDD cases and controls. However, BPD patients carrying at least one rs2230912G-allele scored higher on both MADRS and HADS-depression scale (nominal p-value was 0.028 and 0.003, respectively). The rs1653625AA genotype was also associated with higher depression scores in the BPD group (nominal p-value of MADRS: 0.019, HADS-depression: 0.017). After correction for multiple testing, the association between rs2230912 and HADS-depression score remained significant in the BPD group (p<0.006); this genetic effect explained 9% of the variance (partial η(2)=0.09). In the MDD group we did not find any significant genetic effect.
  
  
  CONCLUSIONS
  The relatively small number of BPD patients warrants for a replication study.
  
  
  CONCLUSIONS
  Our genetic association study supports the association between P2RX7 gene and severity of depressive symptoms in BPD patients.
authors.affiliation: Department of Clinical and Theoretical Mental Health, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Halmai
authors.forename: Peter
authors.initials: P
authors.lastname: Dome
authors.forename: Andrea
authors.initials: A
authors.lastname: Vereczkei
authors.forename: Omar
authors.initials: O
authors.lastname: Abdul-Rahman
authors.forename: Anna
authors.initials: A
authors.lastname: Szekely
authors.forename: Xenia
authors.initials: X
authors.lastname: Gonda
authors.forename: Gabor
authors.initials: G
authors.lastname: Faludi
authors.forename: Maria
authors.initials: M
authors.lastname: Sasvari-Szekely
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Nemoda
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D058486:Receptors, Purinergic P2X7
keywords: BPD:; Bipolar disorder; Depression symptom severity; Genetic association analysis; HADS:; Hospital Anxiety and Depression Scale; MADRS:; MDD:; Major depressive disorder; Montgomery–Åsberg Depression Rating Scale; P2RX7:; Purinergic receptor; SNP:; bipolar disorder; major depressive disorder; purinergic receptor P2X, ligand-gated ion channel, 7; single nucleotide polymorphism