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P.3.01 Association of P2RX7 polymorphism with depression in diabetic patients with poor glycemic control
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Clinical neuropsychopharmacology
Posters P.3.01 Association of P2RX7 polymorphism with depression in diabetic patients with poor glycemic control O. Abdul Rahman1 ° , G. Nagy2 , A. Mate2 , A. Somogyi2 , M. Sasvari-Szekely1 , Z. Nemoda1 . 1 Semmelweis University, Department of Medical Chemistry Molecular Biology and Pathobiochemistry, Budapest, Hungary; 2 Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary Diabetes mellitus and major depression are both public health concerns and the co-occurrence of these illnesses is frequent. Depressive episodes in diabetic patients have a negative effect on the management of diabetes mellitus, therefore, screening for depressive symptoms in this population is highly relevant. It could be hypothesized that hyperglycemia acting as an environmental risk factor might cause the manifestation of depression in patients genetically predisposed to affective disorders. Serotonergic polymorphisms have been identified as genetic risk factors for depression. Moreover, the Gln460Arg polymorphism of the P2RX7 gene coding for a purinergic ligand-gated ion channel, was also linked to bipolar and unipolar depression. We investigated the impact of serotonergic candidate polymorphisms of the tryptophan-hydroxylase-2 and serotonin transporter genes, as well as of the P2RX7 SNP (rs2230912) on depressive symptoms of diabetic patients. We assumed that genetic influence would be stronger in the “poor glycemic control” group compared to the “good glycemic control” group. After excluding patients with current antidepressant medication, data on depressive symptoms and HbA1C levels were accessible for 218 patients (male 48.2%, female 51.8%; type 1 DM 10%, type 2 DM 90%; age at testing 58.0±13.6 years). Depressive and anxiety symptoms were assessed by self-rated questionnaires Hospital Anxiety and Depression Scale (HADS) and the 13-item short Beck Depression Inventory. Patients with HbA1C levels equal or below 7% were considered to have good glycemic control (GC group, n = 81), those who had HbA1C over 7% were put in the poor glycemic control group (PC group, n = 137). The demographic variables
did not differ between the two groups. The genetic effects of candidate polymorphisms were assessed by ANOVA. After correcting for multiple testing we did not observe any main effect of the serotonergic polymorphisms or the glycemic control. However, the P2RX7 Gln460Arg SNP did have a significant effect on the depressive symptoms and a tendency was observed on the anxiety scale, as well. Patients carrying the G-allele (Arg-variant) had higher scores on the HADS depression scale (p = 0.011). This association was only seen in the PC group (p = 0.010) but not in the GC group (p = 0.192). Since the GG genotype is rare, we repeated the analysis using two different approaches, namely leaving out the GG group from the analysis (AA vs. AG, p = 0.007) as well as grouping it together with the AG group (AA vs. AG + GG, p = 0.003), because the G-alle was indicated as a risk factor in mood disorders earlier. Our results support the role of the P2RX7 G-allele in the development of depression and emphasizes the importance of good glycemic control, acting as a potential protective environmental factor in diabetic patients. This work was supported by Hungarian funds ETT-448/2006 and KPI-HEF_06_1-SZER_POL. Reference(s) [1] Zigmond AS, Snaith RP, 1983, The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6), 361−70. [2] Lucae S, Salyakina D, Barden N, Harvey M, Gagne B, Labbe M, Binder EB, Uhr M, Paez-Pereda M, Sillaber I, Ising M, Bruckl T, Lieb R, Holsboer F, Muller-Myhsok B, 2006, P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum Mol Genet 15(16), 2438−45.
Clinical neuropsychopharmacology
Posters P.3.01 Association of P2RX7 polymorphism with depression in diabetic patients with poor glycemic control O. Abdul Rahman1 ° , G. Nagy2 , A. Mate2 , A. Somogyi2 , M. Sasvari-Szekely1 , Z. Nemoda1 . 1 Semmelweis University, Department of Medical Chemistry Molecular Biology and Pathobiochemistry, Budapest, Hungary; 2 Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary Diabetes mellitus and major depression are both public health concerns and the co-occurrence of these illnesses is frequent. Depressive episodes in diabetic patients have a negative effect on the management of diabetes mellitus, therefore, screening for depressive symptoms in this population is highly relevant. It could be hypothesized that hyperglycemia acting as an environmental risk factor might cause the manifestation of depression in patients genetically predisposed to affective disorders. Serotonergic polymorphisms have been identified as genetic risk factors for depression. Moreover, the Gln460Arg polymorphism of the P2RX7 gene coding for a purinergic ligand-gated ion channel, was also linked to bipolar and unipolar depression. We investigated the impact of serotonergic candidate polymorphisms of the tryptophan-hydroxylase-2 and serotonin transporter genes, as well as of the P2RX7 SNP (rs2230912) on depressive symptoms of diabetic patients. We assumed that genetic influence would be stronger in the “poor glycemic control” group compared to the “good glycemic control” group. After excluding patients with current antidepressant medication, data on depressive symptoms and HbA1C levels were accessible for 218 patients (male 48.2%, female 51.8%; type 1 DM 10%, type 2 DM 90%; age at testing 58.0±13.6 years). Depressive and anxiety symptoms were assessed by self-rated questionnaires Hospital Anxiety and Depression Scale (HADS) and the 13-item short Beck Depression Inventory. Patients with HbA1C levels equal or below 7% were considered to have good glycemic control (GC group, n = 81), those who had HbA1C over 7% were put in the poor glycemic control group (PC group, n = 137). The demographic variables
did not differ between the two groups. The genetic effects of candidate polymorphisms were assessed by ANOVA. After correcting for multiple testing we did not observe any main effect of the serotonergic polymorphisms or the glycemic control. However, the P2RX7 Gln460Arg SNP did have a significant effect on the depressive symptoms and a tendency was observed on the anxiety scale, as well. Patients carrying the G-allele (Arg-variant) had higher scores on the HADS depression scale (p = 0.011). This association was only seen in the PC group (p = 0.010) but not in the GC group (p = 0.192). Since the GG genotype is rare, we repeated the analysis using two different approaches, namely leaving out the GG group from the analysis (AA vs. AG, p = 0.007) as well as grouping it together with the AG group (AA vs. AG + GG, p = 0.003), because the G-alle was indicated as a risk factor in mood disorders earlier. Our results support the role of the P2RX7 G-allele in the development of depression and emphasizes the importance of good glycemic control, acting as a potential protective environmental factor in diabetic patients. This work was supported by Hungarian funds ETT-448/2006 and KPI-HEF_06_1-SZER_POL. Reference(s) [1] Zigmond AS, Snaith RP, 1983, The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6), 361−70. [2] Lucae S, Salyakina D, Barden N, Harvey M, Gagne B, Labbe M, Binder EB, Uhr M, Paez-Pereda M, Sillaber I, Ising M, Bruckl T, Lieb R, Holsboer F, Muller-Myhsok B, 2006, P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum Mol Genet 15(16), 2438−45.