Association of ANKK1 polymorphism with schizophrenia: negative findings from a genetic approach

Objective. Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of schizophrenia. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. Variants of ANKK1, specifically rs2734849, may function to affect DRD2 expression and density via regulating the transcription factor NF-κB. We examined whether the functional polymorphism ANKK1 rs2734849 is associated with schizophrenia. Methods. We recruited 468 patients with schizophrenia (235 women / 233 men) and 126 healthy individuals (62 women / 44 men) in Russian population of Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with “Step One Plus”, using the kit “TaqMan SNPGenotyping Assay” (Applied Biosystems, USA). Statistical analysis was carried out using the SPSS software package for Windows, version 21.0. Genotype and allele frequencies were compared between groups of schizophrenia patients and healthy controls using the χ2 , Fisher tests. Results. The average age of patients with schizophrenia in the general group was 42.1 ± 12.4 years, in the group of men with schizophrenia - 37.8 ± 11.9 years, in the group of women with schizophrenia - 45.2 ± 13.9 years. The duration of the disease in the general group was 13 (6; 22), in the group of men with schizophrenia 11 (5; 18), in the group of women with schizophrenia 15 (7; 26), Me values were indicated (25% Q - 75% Q). The results on the allele frequencies of ANKK1 rs2734849 obtained for the control group in our study (rs2734849 MAF 45%) are comparable with the data for Europeoids (MAF 50%) presented in the 1000 Genomes project. The frequency of genotypes (р=0.37) and alleles (р=0.73) of the polymorphic variant ANKK1 rs2734849 in patients with schizophrenia did not differ from those in control subjects. Comparison of the ANKK1 rs2734849 genotypes and alleles distribution in the groups of men and women with schizophrenia, as well as a comparison of these groups with the corresponding by sex control persons, did not reveal statistically significant differences. Perhaps this is due to the insufficient size of the group of healthy controls. It is possible due to the complex nature of the pathophysiological processes underlying schizophrenia. Conclusion. The functional polymorphism rs2734849 in the ANKK1 gene was not associated with schizophrenia in Russian population of Siberian region.

шизофрения, полиморфизм, ANKK1, schizophrenia, polymorphism, ANKK1