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

被引:0
作者
Alfimova M.V. [1 ]
Kondratyev N.V. [1 ]
Golov A.K. [1 ]
Golubev S.A. [1 ]
Galaktionova D.Y. [2 ]
Nasedkina T.V. [2 ]
Golimbet V.E. [1 ]
机构
[1] Mental Health Scientific Center, Moscow
[2] Institute of Molecular Biology, Russian Academy of Sciences, Moscow
关键词
cognitive deficit; DNA methylation; gene; PANSS; RELN; rs7341475; schizophrenia;
D O I
10.1007/s11055-019-00838-5
中图分类号
学科分类号
摘要
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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
引用
收藏
页码:1061 / 1066
页数:5
相关论文
共 36 条
  • [1] Guidotti A., Grayson D.R., Caruncho H.J., Epigenetic RELN dysfunction in schizophrenia and related neuropsychiatric disorders, Front. Cell. Neurosci., 10, (2016)
  • [2] Tost H., Weinberger D.R., RELN rs7341475 and schizophrenia risk: confusing, yet somehow intriguing, Biol. Psychiatry, 69, 5, (2011)
  • [3] Shifman S., Johannesson M., Bronstein M., Et al., Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women, PLoS Genetics, 4, 2, (2008)
  • [4] Liu Y., Chen P.L., McGrath J., Et al., Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women, Psychiatr. Genet., 20, 4, pp. 184-186, (2010)
  • [5] Galaktionova D.Y., Gareeva A.E., Khusnutdinova E.K., Nasedkina T.V., Association of polymorphic markers of the SLC18A1, TPH1, and RELN genes with the risk of developing the paranoid form of schizophrenia, Mol. Biol. (Mosk.), 48, 4, pp. 629-639, (2014)
  • [6] Chen N., Bao Y., Xue Y., Et al., Meta-analyses of RELN variants in neuropsychiatric disorders, Behav. Brain Res., 332, pp. 110-119, (2017)
  • [7] Wedenoja J., Tuulio-Henriksson A., Suvisaari J., Et al., Replication of association between working memory and reelin. A potential modifi er gene in schizophrenia, Biol. Psychiatry, 67, 10, pp. 983-991, (2010)
  • [8] Wedenoja J., Loukola A., Tuulio-Henriksson A., Et al., Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families, Mol. Psychiatry, 13, 7, pp. 673-684, (2008)
  • [9] Baune B.T., Konrad C., Suslow T., Et al., The reelin (RELN) gene is associated with executive function in healthy individuals, Neurobiol. Learn. Mem., 94, 4, pp. 446-451, (2010)
  • [10] Ovadia G., Shifman S., The genetic variation of RELN expression in schizophrenia and bipolar disorder, PLoS One, 6, 5, (2011)