Relationship Between the rs7341475 Polymorphism and DNA Methylation in the Reelin Gene and Schizophrenia Symptoms

Abstract

Objectives. To identify relationships between the rs7341475 polymorphism and methylation of the reelin gene on the one hand and the severity of schizophrenia symptomatology and the neuropsychological indicator – semantic verbal fluency (VF) – on the other. Materials and methods. Genotypes at the rs7341475 locus were determined in 556 patients with schizophrenia spectrum disorders. PANSS evaluations were obtained for 549 of these patients and 221 were tested for semantic VF. The relationship between methylation of the reelin 5’ region and promotor and the severity of PANSS syndromes and VF was assessed using data from 35 patients using the five-factor PANSS model. Results. A relationship was found between genotype at the rs7341475 locus and PANSS measures (a sex-genotype interaction effect: F = 2.70, p = 0.020). Male homozygotes for the common G allele showed the lowest levels of positive syndrome. Verbal fluency was linked with the characteristics of the methylation of the reelin gene promoter. Conclusions. The results obtained here suggest that the rs7341475 polymorphism may be related to variation in positive symptomatology in men. At the same time, the pattern of methylation of the reelin gene is important for retention of VF – with higher levels of methylation in the transcription initiation site and low levels in the distal part of the promoter.