Association of MTHFR 677C&gt;T and 1298A&gt;C polymorphisms with susceptibility to autism: A systematic review and meta-analysis

Sadeghiyeh, Tahereh; Dastgheib, Seyed Alireza; Mirzaee-Khoramabadi, Khadijeh; Morovati-Sharifabad, Majid; Akbarian-Bafghi, Mohammad Javad; Poursharif, Zahra; Mirjalili, Seyed Reza; Neámatzadeh, Hossein

doi:10.1016/j.ajp.2019.09.016

Cited by 33 publications

(27 citation statements)

References 36 publications

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“…However, in subgroup analysis, the significant association was only found among Caucasians but not in East Asians and Africans. The results of their subgroup analysis were inconsistent with the above meta-analysis (44), probably because only three studies were included in East-Asian countries and the sample size was insufficient. However, Sadeghiyeh et al (44) also searched some Chinese databases, so there were more studies conducted in Asia.…”

Section: Discussionmentioning

confidence: 86%

“…The results of their subgroup analysis were inconsistent with the above meta-analysis (44), probably because only three studies were included in East-Asian countries and the sample size was insufficient. However, Sadeghiyeh et al (44) also searched some Chinese databases, so there were more studies conducted in Asia. Therefore, the finding that there was a significant association between C677T and autism risk among Asians was more convincing, which is in line with our results as well.…”

Section: Discussionmentioning

confidence: 86%

“…In 2019, Sadeghiyeh et al (44) in a meta-analysis of 18 studies evaluated the association between MTHFR 677C>T polymorphism and autism risk. Of the 18 studies, eight were conducted in Caucasian countries, three studies were in African population, and six studies were in Asian population.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2021

Front. Psychiatry

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Objective: To explore the association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with birth body mass and risk of autism in Chinese Han population.Methods: A total 1,505 Chinese Han autism patients were recruited, using the Diagnostic and Statistical Manual of Mental Disorders, 4th revised version (DSM-IV-R) diagnostic criteria for autism, and 1,308 sex-matched healthy controls were also enrolled for the study. All the participants' birth body masses were counted according to the medical records. The MTHFR C677T genotypes were detected using the polymerase chain reaction-restrict fragment length polymorphism (PCR-RFLP) method. The association between C677T polymorphism, birth body mass, and risk of autism were analyzed using the chi-square tests.Results: The present study found that the MTHFR 677T was significantly associated with risk of autism [P = 0.004, odds ratio (OR) = 1.18, 95% CI = 1.02–1.29). The autism children more frequently showed low birth body mass (<2.5 kg) than healthy control subjects (8.6 vs. 5.3%, P = 0.001, OR = 1.67, 95% CI = 1.24–2.26). The interactive effects between MTHFR 677T and low birth body mass (P = 0.0001, OR = 2.18, 95% CI = 1.44–3.32) were also significantly associated with risk of autism.Conclusions: The MTHFR C677T polymorphism and low birth body mass may be associated with risk of autism in Chinese Han population.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 86%

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

Zhang

et al. 2021

Front. Psychiatry

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“…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. Given that China is a vast territory characterized by prominent regional differences, it is worth conducting a subgroup analysis of the Chinese population.…”

Section: Introductionmentioning

confidence: 85%

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

Liu

Che

et al. 2021

Front. Pediatr.

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Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible “false positive report,” we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

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“…Notably, a key enzyme for regulating the availability of folate for either DNA synthesis or DNA methylation is methylenetetrahydrofolate reductase (MTHFR). Remarkably, some MTHFR genetic polymorphisms have been associated with ASD risk [134,171]. This is another example of how inadequate diet or gut dysbiosis may mimic genetic defects promoting the onset of ASD.…”

Section: Microbiome In the Crosstalk Between Immune System Gut And Brainmentioning

confidence: 99%

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift

Panisi

Guerini

Abruzzo

et al. 2021

JPM

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The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called ‘First 1000 Days’) are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

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Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis

Cited by 33 publications

References 36 publications

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

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

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

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift

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