Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies

Ignacio Hernández-García, Antonio-Javier Chamorro, Hugo Guillermo Ternavasio- de la Vega, Cristina Carbonell, Miguel Marcos and José-Antonio Mirón-Canelo
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Ignacio Hernández-García: Department of Preventive Medicine and Public Health, Lozano Blesa University Clinical Hospital of Zaragoza, Calle San Juan Bosco 15, 50009 Zaragoza, Spain
Antonio-Javier Chamorro: Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
Hugo Guillermo Ternavasio- de la Vega: Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
Cristina Carbonell: Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
Miguel Marcos: Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
José-Antonio Mirón-Canelo: Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain

IJERPH, 2020, vol. 17, issue 21, 1-16

Abstract: Autistic spectrum disorder (ASD) is a complex neurodevelopmental disability with a genetic basis, and several studies have suggested a potential role of the reelin gene (RELN) in ASD susceptibility. Accordingly, genetic association studies have explored this potential association, but the results have been controversial thus far. For this reason, we assessed the association of four genetic variants of RELN (the 5′UTR CGG triplet repeat and polymorphisms rs736707, rs362691, and rs2229864) with ASD by means of a systematic review and meta-analysis. We retrieved studies comparing the distribution of the above-mentioned genetic variants between ASD patients and healthy controls. A meta-analysis was conducted using a random effects model, and calculations of the odds ratios (ORs) and confidence intervals (CIs) were performed. A sensitivity analysis and tests to determine the heterogeneity of the results were also performed. Eleven previous studies fulfilled the inclusion criteria and analyzed the association of the above-mentioned genetic variants and ASD. We did not find any significant association between the allele or genotype frequencies of the analyzed polymorphisms and ASD, and large heterogeneity was found for the rs736707 polymorphism. Moreover, no significant differences were found between the 5′UTR triplet repeat and this disorder. In light of current evidence, no single genetic variant within this gene is clearly associated with the development of ASD, and ethnic differences may explain part of the observed heterogeneity. Larger studies among different ethnic groups are needed to establish the role of specific genetic variants within RELN in the etiology of this disorder.

Keywords: reelin; autistic spectrum disorder; polymorphism; genetics; meta-analysis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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