<p>Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community</p>

Abstract

Purpose: 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

Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism

“…Consistent with this, a growing body of evidence suggests that the severity of autistic symptoms as a whole may be associated with increased levels of homocysteine associated with aggravation of dopamine deficiency (Carpita et al, 2023;Dangmann, 2023;Majhi et al, 2023). According to our data, rs1801133 of MTHFR, despite being less prevalent in our sample (12.9%) than in another cohort of Saudi children with ASD (36%) (Arab and Elhawary, 2019), was associated with a significant decrease in 9-OH-RIS and total active moiety levels, yet no evident impact was observed on RIS plasma exposure. The decreased concentration of the active moiety and a more pronounced effect on 9-OH-RIS could be explained by several factors.…”

Association Between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population

“…Previous studies have mainly focused on the influence of the MTHFR C677T on autism susceptibility, but the findings are still inconclusive. For example, (15) reported a correlation between MTHFR C677T polymorphism and a higher susceptibility to ASD, but this is not consistent with the findings of Dos Santos et al (16). A recent meta-analysis (17) suggested a significant association between them overall and by ethnicity, and thus the MTHFR C677T polymorphism could be used as a diagnostic marker of autism by ethnic background.…”

Phenotypic variability to medication management: an update on fragile X syndrome

“…Several studies have investigated modifier genes and their relationship with behavioral features of the FXS phenotype (e.g., epilepsy, aggression, autistic features) [ 99 – 103 ]. One study found that the Val66Met polymorphism in the brain-derived neurotrophic factor ( BDNF ) gene may lessen the epilepsy phenotype in FXS patients, as this polymorphism can affect cerebral anatomy [ 104 ] and fragile X-associated neuropsychiatric disorders (FXAND) [ 99 – 107 ]. Evidence has been conflicting on whether variations in genes such as SLC6A4 (MIM 182138), MAOA (MIM 309850) , and COMT (MIM 116790) genes affect the severity of aggression, self-injury, and stereotypic behaviors in males with FXS [ 108 ].…”