Female gender specific association of the Reelin (RELN) gene rs7341475 variant with schizophrenia
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RELN gene encodes a large extracellular matrix protein which is critical for neuronal migration, cell positioning and cell–cell interactions. It also controls the synaptic plasticity of neurons for initiation and maintenance of long term potentiation. The aim of this study is to investigate the association of RELN rs7341475 variant with schizophrenia. Genomic DNA isolation was performed from 105 schizophrenic patients and 137 healthy controls to determine RELN rs7341475 genotypes. Genotype and allele frequencies were determined by a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. Statistical analysis was performed using χ2 test. The frequencies for G allele were 79.5% in cases and 81.0% in controls, for A allele 20.5% in cases and 19.0% in controls in the overall population. The genotype frequencies of the RELN gene rs7341475 variant were GG; 63.8%, GA; 31.4% and AA; 4.8% in cases, GG; 63.5%, GA; 35.0% and AA; 1.5% in controls in the overall population. There was no statistically significant association between the rs7341475 variant of RELN gene and schizophrenia in the overall population (χ2 = 2.473, p = 0.290). In the gender specific analysis, female gender specific association was only found. The RELN rs7341475 variant GG genotype was significantly associated with schizophrenia (p = 0.034, OR 2.760, 95% CI 1.058–7.197) and A allele was protective against schizophrenia (p = 0.034, OR 0.362, 95% CI 0.139–0.945). All cases and controls were in Hardy–Weinberg equilibrium (p > 0.05). Population size can be increased to improve the statistical power. Moreover, other RELN gene variants which are especially involved in neuronal migration and epigenetic regulation may be analyzed for revealing the complex genetic architecture of schizophrenia. In conclusion, there was only association between the RELN rs7341475 variant and schizophrenia in the female gender in a Turkish population.
KeywordsRELN gene Schizophrenia Polymorphism rs7341475 Female gender Specific association Turkish population
This study was supported by Kocaeli University, Project No: 2011/68 to AS.
Compliance with ethical standards
Conflict of interest
No conflict of interest exists.
- 5.Shifman S, Johannesson M, Bronstein M, Chen SX, Collier DA, Craddock NJ, Kendler KS, Li T, O’Donovan M, O’Neill FA, Owen MJ, Walsh D, Weinberger DR, Sun C, Flint J, Darvasi A (2008) Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet 4(2):e28CrossRefGoogle Scholar
- 7.Absil P, Pinxten R, Balthazart J, Eens M (2003) Effects of testosterone on Reelin expression in the brain of male European starlings. Cell Tissue Res 312:81–93Google Scholar
- 12.Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E (1998) A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 95(26):15718–15723CrossRefGoogle Scholar
- 13.Guidotti A, Auta J, Davis JM, Dong E, Gavin DP, Grayson DR, Sharma RP, Smith RC, Tueting P, Zhubi A (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 57(11):1061–1069CrossRefGoogle Scholar
- 14.Ruscio AM, Hallion LS, Lim CCW, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J, Andrade LH, Borges G, Bromet EJ, Bunting B, Caldas de Almeida JM, Demyttenaere K, Florescu S, de Girolamo G, Gureje O, Haro JM, He Y, Hinkov H, Hu C, de Jonge P, Karam EG, Lee S, Lepine JP, Levinson D, Mneimneh Z, Navarro-Mateu F, Posada-Villa J, Slade T, Stein DJ, Torres Y, Uda H, Wojtyniak B, Kessler RC, Chatterji S, Scott KM (2017) Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry 74:465–475CrossRefGoogle Scholar
- 20.Dazzo E, Fanciulli M, Serioli E, Minervini G, Pulitano P, Binelli S, Di Bonaventura C, Luisi C, Pasini E, Striano S, Striano P, Coppola G, Chiavegato A, Radovic S, Spadotto A, Uzzau S, La Neve A, Giallonardo AT, Mecarelli O, Tosatto SC, Ottman R, Michelucci R, Nobile C (2015) Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy. Am J Hum Genet 96(6):992–1000CrossRefGoogle Scholar
- 22.Lammert DB, Howell BW (2016) RELN mutations in autism spectrum disorder. Front Cell Neurosci 31(10):84Google Scholar
- 24.Wedenoja J, Loukola A, Tuulio-Henriksson A, Paunio T, Ekelund J, Silander K, Varilo T, Heikkilä K, Suvisaari J, Partonen T, Lönnqvist J, Peltonen L (2008) Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families. Mol Psychiatry 13(7):673–684CrossRefGoogle Scholar
- 27.http://www.ncbi.nlm.nih.gov/projects/SNP (Last accession date: 25.07.2017)