Study of genotype–phenotype correlation of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in a sample of Egyptian autistic children

Shawky, Rabah M.; El-Baz, Farida; Kamal, Tarek M.; Elhossiny, Reham M.; Ahmed, Mona A.; Nady, Ghada H. El

doi:10.1016/j.ejmhg.2014.05.004

Cited by 16 publications

(15 citation statements)

References 32 publications

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“…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.…”

Section: Discussioncontrasting

confidence: 99%

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

Arab¹,

Elhawary²

2019

NDT

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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

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Section: Discussioncontrasting

confidence: 99%

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

Arab¹,

Elhawary²

2019

NDT

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“…This is in agreement with previous reports (20). C667T polymorphism genotyping was consistent with the study of Elif et al (19) that revealed the heterozygote 667CT as the most prevalent genotype among patients.…”

Section: Discussionsupporting

confidence: 94%

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

et al. 2017

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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.

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“…Rai et al [ 26 ] investigated 1978 cases and 7257 controls (Caucasians: 1355 cases and 6460 controls; Asians: 623 cases and 797 controls) in 13 studies [ 18 , 22 , 27 , 28 , 31 , 33 , 35 , 43 , 44 , 46 , 48 , 50 ] and found that C677T polymorphism of MTHFR is a risk factor for ASD susceptibility as well [ 26 ]. Similarly, the current meta-analysis enrolled 2609 cases and 7496 controls (Caucasian: 1786 cases and 6499 controls, Asian: 823 cases and 997 controls) from 15 selected literature [ 9 , 18 , 22 , 26 – 28 , 31 , 32 , 33 , 35 , 43 , 47 , 48 , 50 ], further confirmed the association between C677T polymorphism of MTHFR and ASD susceptibility.…”

Section: Discussionsupporting

confidence: 70%

“…In the present meta-analysis, eight of the selected articles [ 18 , 22 , 32 , 35 , 36 , 43 , 44 , 47 , 50 ] had enrolled 1961 cases and 1652 controls (Caucasians: 1387 cases and 991 controls, Asians: 574 cases and 661 controls), and it was recognized that A1298C polymorphism of MTHFR was not correlated with ASD susceptibility. However, Khalil et al (42 cases and 48 controls) [ 49 ] and El-Baz et al (31 cases and 39 controls) [ 32 ] revealed that MTHFR A1298C polymorphism represented a risk factor in association with ASD.…”

Section: Discussionmentioning

confidence: 99%

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

Qiu

Shi

et al. 2020

BMC Pediatr

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Background Autism spectrum disorder (ASD) is becoming increasingly prevalent of late. Methylenetetrahydrofolate reductase (MTHFR) has a significant role in folate metabolism. Owing to the inconsistencies and inconclusiveness on the association between MTHFR single nucleotide polymorphism (SNP) and ASD susceptibilities, a meta-analysis was conducted to settle the inconsistencies. Methods For this meta-analysis, a total of 15 manuscripts published up to January 26, 2020, were selected from PubMed, Google Scholar, Medline, WangFang, and CNKI databases using search terms “MTHFR” OR “methylenetetrahydrofolate reductase” AND “ASD” OR “Autism Spectrum Disorders” OR “Autism” AND “polymorphism” OR “susceptibility” OR “C677T” OR “A1298C”. Results The findings of the meta-analysis indicated that MTHFR C677T polymorphism is remarkably associated with ASD in the five genetic models, viz., allelic, dominant, recessive, heterozygote, and homozygote. However, the MTHFR A1298C polymorphism was not found to be significantly related to ASD in the five genetic models. Subgroup analyses revealed significant associations of ASD with the MTHFR (C677T and A1298C) polymorphism. Sensitivity analysis showed that this meta-analysis was stable and reliable. No publication bias was identified in the associations between MTHFRC677T polymorphisms and ASD in the five genetic models, except for the one with regard to the associations between MTHFRA1298C polymorphisms and ASD in the five genetic models. Conclusion This meta-analysis showed that MTHFR C677T polymorphism is a susceptibility factor for ASD, and MTHFR A1298C polymorphism is not associated with ASD susceptibility.

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Study of genotype–phenotype correlation of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in a sample of Egyptian autistic children

Cited by 16 publications

References 32 publications

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

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

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

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

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