Study of C677T variant of methylene tetrahydrofolate reductase gene in autistic spectrum disorder Egyptian children

Abstract

Background: Autism spectrum disorders (ASD) is a heterogeneous neurodevelopmental disease, various articles reported that dysfunctional folate-methionine pathway enzymes might assume a paramount part in the pathophysiology of autism. Methylene tetrahydrofolate reductase (MTHFR) is a basic catalyst for this pathway, also MTHFR gene C677T variant accounted as a risk factor of autism.Objective: The present study aimed to investigate the association of MTHFR gene rs1801133(C677T) variant among Egyptian autistic children. Methods: The study included 78 autistic children, and 80 matched healthy control children. Full clinical and radiological examinations were conducted. MTHFR genetic variant, rs1801133(C677T) was studied by using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) methods followed by direct sequencing technique. Results: MTHFR (C677T) allele frequency was found to be higher significantly in ASD cases compared with nonautistic children. Also, we had a higher distribution of combined CT + TT genotypes among autistic patients with consanguinity and family history of psychological disease. In Gastrointestinal tract (GIT) and sleep disorders showed a higher distribution of hetero CT genotype as well as combined CT + TT genotypes. Conclusion: This study demonstrated a role of MTHFR gene (C667T) variant with the increased risk for ASD. K E Y W O R D S autism, MTHFR, variant, C667T

Association Study of MTHFR C677T Polymorphism and Birth Body Mass With Risk of Autism in Chinese Han Population

“…The folic acid metabolic-rate-limiting enzyme, methylenetetrahydrofolate reductase (MTHFR), also may play an important regulatory role in neurodevelopmental disorders such as autism (19,20). At the same time, there were also many reports that perinatal environmental factors such as low birth body mass may increase the risk of autism (10)(11)(12)(13)(14)(15)(16). The results of the present study also further confirmed some above-mentioned findings.…”

“…In a large-scale cross-country cohort study of more than two million people carried out by Ban et al (9), 22,156 of them were diagnosed with autism, with heritability of ∼80% but without support for maternal effect and environmental impact, indicating that the changes in the occurrence rate of autism in this population were mainly attributed to genetic impact. However, new evidence show that environmental factors also increase the risk of autism, such as prenatal estrogen, maternal body mass index (BMI), perinatal complications, birth season, birth body mass, and other environmental risk factors, as well as the interaction between heredity and environment, which are also related to the risk of autism (10)(11)(12)(13)(14)(15)(16).…”

Folic Acid and Autism: A Systematic Review of the Current State of Knowledge

“…On the other hand, an important consideration clarified the role of the MTHFR C677T polymorphism and ASDs (Table 3) [53,55,56,59]. A population-based case-control study in Chinese Han assessed the frequency of genotype MTHFR 677TT in 372 children.…”

Association Between HLA-B Polymorphisms and Autism Spectrum Disorder in Chinese Population

“…Also, a number of studies identified that several singlenucleotide polymorphisms (SNP) in different genes had relationship with ASD children. For example, SNPs in tryp-tophan hydroxylase 2 (TPH2), oxytocin receptor (OXTR), neuroligin1 (NLGN1) and methylenetetrahydrofolate reductase (MTHFR) were all found to have an association with ASD in diverse studies (10)(11)(12)(13). In the past three decades, HLA gene complex received increasing attention.…”