Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder

Abstract

BackgroundAutism is currently known as “a behaviorally defined syndrome” manifested as impairment in social communication, repetitive routines and restricted interests. There is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle.AimThe aim of this study was to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients.MethodsThis case-control study was carried out from 2013 through 2015. The study included 31 children with autism and 39 children in a normal control group, the mean age of patients and control was comparable (4.5 years± 2) with males predominant in both groups. We used DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis. Data were analyzed by SPSS version 11, using Chi-Square, independent-samples t-test, and ANOVA.ResultsThere was significant relationship between low birth weight and occurrence of autism (p<0.01), and between delayed motor and social milestones in cases of autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6% normal AA (wild) type and Allele C was detected in patients more than in control (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and 12.9% for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A–C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS).ConclusionThere is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on a larger scale to explore other genes polymorphisms that may be associated with autism, to correlate the genetic basis of autism.

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

“…Of six studies in the literature, four showed significant associations between the allelic variants and genotypic distributions of the 1298A>C rs1801131 SNP and ASD. 20,40,41,44 The other two studies showed no associations between this SNP and ASD 17,18 (Table 8). James et al 42 reported that several genes were linked to folate/homocysteine pathways in ASD cases but did not report any significant associations with MTHFR 677C>T and MTHFR 1298A>C when these SNPs were assessed separately.…”

“…ASD studies have shown conflicting results regarding the susceptibility of candidate genes to CARS scores. 57 El-Baz et al 44 reported that the heterozygotes 677C/T and 1298A/C were found equally (46.2%) in ASD cases with severe CARS scores, and no significant differences were found between severe and mild/moderate cases, according to CARS scores. However, in contrast to previous studies in Egyptian populations, 44,58 our study in the Saudi population showed a significant difference in the frequency of the 677C>T and 1298A>C SNPs when comparing CARS scores <37 and CARS scores ≥37 (P = 0.001, and P = 0.0014) in the non-additive models.…”

Linking genetics to epigenetics: The role of folate and folate‐related pathways in neurodevelopmental disorders

“…96 However, more studies should be performed on this polymorphism in ADHD before reaching a final conclusion about the possible role of MTHFR C677T polymorphism as a risk factor in this neurodevelopmental disorder. In relation to the MTHFR A1298C polymorphism a significant association between the C allele and/or the AC and CC genotypes was found in two 82,87 out of five association studies on ASD (Table1). 74,76,79,82,87 RFC1 A80G polymorphism was studied in ASD and control populations by four groups.…”

Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis

“…Guo et al [ 31 ] evidenced that MTHFR C677T polymorphism is a risk factor for ASD among Chinese Han children [ 31 ]. El-baz et al [ 32 ] recognized a significant correlation between MTHFR C677T polymorphisms and ASD among Egyptian children [ 32 ]. Nonetheless, Dos Santos et al [ 28 ] found no correlation between MTHFR C677T polymorphism and ASD [ 28 ].…”

“…Nonetheless, Dos Santos et al [ 28 ] found no correlation between MTHFR C677T polymorphism and ASD [ 28 ]. Studies by Khalil et al [ 33 ] and El-baz et al [ 32 , 34 ] describe MTHFR A1298C polymorphism to represent a risk factor in correlation with ASD among Egyptian children. On the contrary, Mohammad et al [ 35 ] evidenced that MTHFR A1298C polymorphism variant allele has no link with any independent risk of ASD [ 35 ].…”