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Association between depression and the Gln460Arg polymorphism of P2RX7 Gene: A dimensional approach.

Hejjas K, Szekely A, Domotor E, Halmai Z, Balogh G, Schilling B, Sarosi A, Faludi G, Sasvari-Szekely M, Nemoda Z

Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.

The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a novel candidate gene for major depressive disorder (MDD) and bipolar disorder (BPD). The proposed risk allele (G-allele) of the rs2230912 polymorphism results in an amino acid change at the 460th position, marking this genetic variation a possibly functional one. Here we present a case-control analysis of 171 patients diagnosed with MDD or BPD and 178 controls, as well as a dimensional approach using the Hospital Anxiety and Depression Scale (HADS) for studying the Gln460Arg polymorphism of the P2RX7 gene as a genetic risk factor in depression. While case-control analysis did not show significant difference between the groups, a significant association was found between the P2RX7 polymorphism and the HADS scales in the clinical group (MANOVA P = 0.001). Both anxiety and depression scores increased as the number of G-allele increased in the genotype groups (ANOVA for HADS-anxiety: P = 0.01, HADS-depression: P < 0.001). A significant interaction of clinical status and the P2RX7 polymorphism was also found for the depression scale (MANOVA P = 0.025, subsequent ANOVA for anxiety: P = 0.252; depression: P = 0.002). Whereas patients with G-allele-present genotypes showed more elevated depression scores, level of depression in the control group was not affected by the P2RX7 genotype. In conclusion, case-control analysis did not reveal significant results, but using a symptom severity scale we could support the association between depressive disorder and the G-allele of the Gln460Arg polymorphism in the P2RX7 gene. (c) 2008 Wiley-Liss, Inc.

Published 10 June 2008 in Am J Med Genet B Neuropsychiatr Genet.
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