P2RX7 Gln460Arg polymorphism is associated with depression among diabetic patients

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Both diabetes mellitus and major depression are public health concerns, and the co-occurrence of these illnesses is highly frequent. Acting as a potential risk factor, hyperglycemia might facilitate the manifestation of depression in patients genetically predisposed to affective disorders. In the present study, candidate polymorphisms of the serotonin transporter, the tryptophan hydroxylase 2 (TPH2) genes, as well as of the brain-derived neurotrophic factor BDNF, and the P2RX7 purinergic receptor genes were analyzed in Hungarian diabetic population. We assumed that genetic influence would be stronger on depressive symptoms in the “poor glycemic control” group (PC: HbA1C > 7%) compared to the “good glycemic control” group (GC: HbA1C ≤ 7%).


After excluding patients with current antidepressant medication, 218 diabetic patients' Hospital Anxiety and Depression Scale (HADS) scores were used in multivariate analysis of variance. Based on the HbA1C levels, 81 patients were in the GC group, and 137 belonged to the PC group.


After correcting for multiple testing, only the association of the P2RX7 Gln460Arg (rs2230912) polymorphism with depressive symptoms remained significant. Patients with the G-allele (Arg-variant) had higher scores on the HADS depression scales (p = 0.007). A gene x glycemic control interaction (p = 0.032) was observed on the anxiety scale at the TPH2 promoter polymorphism: the -703T-allele decreased anxiety scores only in the GC group (p = 0.008).


Our results support the role of the P2RX7 rs2230912 G-allele in the development of depression and emphasize the importance of good glycemic control, acting as a potential protective factor in diabetic patients.

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