P2RX7 Gln460Arg polymorphism is associated with depression among diabetic patients.
OBJECTIVE
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<or=7%).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Nagy
Geza
G
Semmelweis University, 2nd Department of Internal Medicine, Budapest, 1088, Szentkiralyi u. 46, Hungary.
Ronai
Zsolt
Z
Somogyi
Aniko
A
Sasvari-Szekely
Maria
M
Rahman
Omar Abdul
OA
Mate
Attila
A
Varga
Timea
T
Nemoda
Zsofia
Z
D001120:Arginine / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D003863:Depression / Q000209:etiology / Q000235:genetics*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D050486:Serotonin Plasma Membrane Transport Proteins; D005973:Glutamine; D001120:Arginine; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase