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Meta-Analysis
. 2020 Oct 30;17(21):8010.
doi: 10.3390/ijerph17218010.

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  1 , Antonio-Javier Chamorro  2   3   4 , Hugo Guillermo Ternavasio-de la Vega  2   3   4 , Cristina Carbonell  2   3   4 , Miguel Marcos  2   3   4 , José-Antonio Mirón-Canelo  4   5
Affiliations
Meta-Analysis

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 et al. Int J Environ Res Public Health. .

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: autistic spectrum disorder; genetics; meta-analysis; polymorphism; reelin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the selection of studies for inclusion in the meta-analysis.
Figure 2
Figure 2
Meta-analysis of the association of reelin gene polymorphisms with autistic spectrum disorder (ASD). (A): Distribution of the genotype CC of the exon 22 polymorphism (rs362691) compared between patients with ASD (cases) and healthy controls under a random effects model. (B): Distribution of the genotype TT of the exon 50 polymorphism (rs2229864) compared between patients with ASD (cases) and healthy controls under a random effects model. (C): Distribution of the genotype TT of the intron 59 polymorphism (rs736707) compared between patients with ASD (cases) and healthy controls under a random effects model.
Figure 2
Figure 2
Meta-analysis of the association of reelin gene polymorphisms with autistic spectrum disorder (ASD). (A): Distribution of the genotype CC of the exon 22 polymorphism (rs362691) compared between patients with ASD (cases) and healthy controls under a random effects model. (B): Distribution of the genotype TT of the exon 50 polymorphism (rs2229864) compared between patients with ASD (cases) and healthy controls under a random effects model. (C): Distribution of the genotype TT of the intron 59 polymorphism (rs736707) compared between patients with ASD (cases) and healthy controls under a random effects model.
Figure 3
Figure 3
Meta-analysis of the association between the polymorphic trinucleotide repeat (CGG/GCC) within the reelin gene and ASD.
See this image and copyright information in PMC

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