Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community

Arwa H Arab,1 Nasser A Elhawary2,3 1Department of Psychology, Faculty of Arts and Humanities, King Abdul-Aziz University, Jeddah 21589, Saudi Arabia; 2Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, Saudi Arabia; 3Department of Molecular Genetics, Medical Ge...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Arab AH, Elhawary NA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	autism spectrum disorder genetic association single nucleotide polymorphism taqman genotyping linkage disequilibrium combined genotypes cars scores Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3fae3aa6c55740bb85ad63bf15be26b3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3fae3aa6c55740bb85ad63bf15be26b3
record_format	dspace
spelling	oai:doaj.org-article:3fae3aa6c55740bb85ad63bf15be26b32021-12-02T12:01:59ZMethylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community1178-2021https://doaj.org/article/3fae3aa6c55740bb85ad63bf15be26b32019-12-01T00:00:00Zhttps://www.dovepress.com/methylenetetrahydrofolate-reductase-gene-variants-confer-potential-vul-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Arwa H Arab,1 Nasser A Elhawary2,3 1Department of Psychology, Faculty of Arts and Humanities, King Abdul-Aziz University, Jeddah 21589, Saudi Arabia; 2Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, Saudi Arabia; 3Department of Molecular Genetics, Medical Genetics Center, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptCorrespondence: Arwa H Arab; Nasser A Elhawary Tel +966 55 369 2180Email naelhawary@uqu.edu.sa; aarab@kau.edu.saPurpose: Several interacting genes or single nucleotide polymorphisms (SNPs) are vulnerable to the risk of autism spectrum disorder (ASD). Here we explored associations between SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene or combined genotypes and the risk of ASD in a Saudi community.Subjects and methods: ASD severity symptoms were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria and scores on the childhood autism rating scale (CARS). Genomic DNA from buccal cells was analyzed for 112 cases and 104 healthy controls using TaqMan genotyping assays of 677C>T rs1801133 and 1298A>C rs1801131 SNPs in the MTHFR gene. SNPStats software was utilized to determine the best interactive model of inheritance of genotypic data.Results: Controls were consistent with Hardy-Weinberg equilibrium in the examined SNPs. Our data showed associations between the 677C>T and 1298A>C SNPs and ASD risk (odds ratio [OR]= 5.2; 95% confidence interval [CI], 3.1–9.8 and OR= 22.2; 95% CI, 7.9–62.3, respectively). Genotype associations of 677C>T and 1298A>C were identified in cases compared with controls (P= 0.0012 and P= 0.0008, respectively). The examined SNPs were significantly associated with ASD cases having ≥37 scores (codominant and recessive models; P= 0.001 and P= 0.0005, respectively). Six combined genotypes—C/C-A/A (42.9%), C/T-A/A (17.9%), C/T-C/C (14.5%), C/T-A/C (10.9%), T/T-C/C (10.9%), and T/T-A/A (3.6%)—were found in ASD cases. Global haplotype analysis showed a significant difference in haplotype distribution between cases and controls (P= 0.00057). The two SNPs were found to be in relatively strong linkage disequilibrium (D`= 0.63, r2= 0.260).Conclusion: Our findings suggest that the 677C>T and 1298A>C SNPs add to each other for potential vulnerability to increase the risk of ASD, particularly if they can be confirmed in larger cohorts along with other genetic/environmental factors. Our study could create reference data for future genetic association studies in the Saudi population and for use by government and health experts to develop regional health management programs.Keywords: Autism spectrum disorder, genetic association, single nucleotide polymorphism, TaqMan genotyping, linkage disequilibrium, combined genotypes, CARS scoresArab AHElhawary NADove Medical Pressarticleautism spectrum disordergenetic associationsingle nucleotide polymorphismtaqman genotypinglinkage disequilibriumcombined genotypescars scoresNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 3569-3581 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism spectrum disorder genetic association single nucleotide polymorphism taqman genotyping linkage disequilibrium combined genotypes cars scores Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	autism spectrum disorder genetic association single nucleotide polymorphism taqman genotyping linkage disequilibrium combined genotypes cars scores Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Arab AH Elhawary NA Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
description	Arwa H Arab,1 Nasser A Elhawary2,3 1Department of Psychology, Faculty of Arts and Humanities, King Abdul-Aziz University, Jeddah 21589, Saudi Arabia; 2Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, Saudi Arabia; 3Department of Molecular Genetics, Medical Genetics Center, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptCorrespondence: Arwa H Arab; Nasser A Elhawary Tel +966 55 369 2180Email naelhawary@uqu.edu.sa; aarab@kau.edu.saPurpose: Several interacting genes or single nucleotide polymorphisms (SNPs) are vulnerable to the risk of autism spectrum disorder (ASD). Here we explored associations between SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene or combined genotypes and the risk of ASD in a Saudi community.Subjects and methods: ASD severity symptoms were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria and scores on the childhood autism rating scale (CARS). Genomic DNA from buccal cells was analyzed for 112 cases and 104 healthy controls using TaqMan genotyping assays of 677C>T rs1801133 and 1298A>C rs1801131 SNPs in the MTHFR gene. SNPStats software was utilized to determine the best interactive model of inheritance of genotypic data.Results: Controls were consistent with Hardy-Weinberg equilibrium in the examined SNPs. Our data showed associations between the 677C>T and 1298A>C SNPs and ASD risk (odds ratio [OR]= 5.2; 95% confidence interval [CI], 3.1–9.8 and OR= 22.2; 95% CI, 7.9–62.3, respectively). Genotype associations of 677C>T and 1298A>C were identified in cases compared with controls (P= 0.0012 and P= 0.0008, respectively). The examined SNPs were significantly associated with ASD cases having ≥37 scores (codominant and recessive models; P= 0.001 and P= 0.0005, respectively). Six combined genotypes—C/C-A/A (42.9%), C/T-A/A (17.9%), C/T-C/C (14.5%), C/T-A/C (10.9%), T/T-C/C (10.9%), and T/T-A/A (3.6%)—were found in ASD cases. Global haplotype analysis showed a significant difference in haplotype distribution between cases and controls (P= 0.00057). The two SNPs were found to be in relatively strong linkage disequilibrium (D`= 0.63, r2= 0.260).Conclusion: Our findings suggest that the 677C>T and 1298A>C SNPs add to each other for potential vulnerability to increase the risk of ASD, particularly if they can be confirmed in larger cohorts along with other genetic/environmental factors. Our study could create reference data for future genetic association studies in the Saudi population and for use by government and health experts to develop regional health management programs.Keywords: Autism spectrum disorder, genetic association, single nucleotide polymorphism, TaqMan genotyping, linkage disequilibrium, combined genotypes, CARS scores
format	article
author	Arab AH Elhawary NA
author_facet	Arab AH Elhawary NA
author_sort	Arab AH
title	Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
title_short	Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
title_full	Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
title_fullStr	Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
title_full_unstemmed	Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
title_sort	methylenetetrahydrofolate reductase gene variants confer potential vulnerability to autism spectrum disorder in a saudi community
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/3fae3aa6c55740bb85ad63bf15be26b3
work_keys_str_mv	AT arabah methylenetetrahydrofolatereductasegenevariantsconferpotentialvulnerabilitytoautismspectrumdisorderinasaudicommunity AT elhawaryna methylenetetrahydrofolatereductasegenevariantsconferpotentialvulnerabilitytoautismspectrumdisorderinasaudicommunity
_version_	1718394741682339840

Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community

Ejemplares similares