Aberrations In Folate Metabolic Pathway And Altered Susceptibility To Autism
Naushad Shaik Mohammad, Jamal Md Nurul Jain, Krishna Prasad Chintakindi, Ram Prakash Singh, Usha S. Naik, Radha Rama Devi Akella
Published 2009 · Biology, Medicine
Download PDFAnalyze on Scholarcy
Objective To investigate whether genetic polymorphisms are the underlying causes for aberrations in folate pathway that was reported in autistic children. Basic methods A total of 138 children diagnosed as autistic based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria and Autism Behavior Checklist scoring and 138 age and sex matched children who are nonautistic were tested for five genetic polymorphisms, that is, cytosolic serine hydroxyl methyl transferase (SHMT1 C1420T), methylene tetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), methionine synthase reductase (MTRR A66G), methionine synthase (MS A2756G) using PCR-restriction fragment length polymorphism methods. Fisher's exact test and logistic regression analysis were used for statistical analyses. Results MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (16.3 vs. 6.5%) with 2.79-fold increased risk for autism [95% confidence interval (CI): 1.58–4.93]. The frequencies of MTRR 66A allele (12.7 vs. 21.0%) and SHMT 1420T allele (27.9 vs. 45.3%) were lower in autistic group compared with nonautistic group with odds ratios 0.55 (95% CI: 0.35–0.86) and 0.44 (95% CI: 0.31–0.62), respectively, indicating reduced risk. MTHFR 1298C-allele frequency was similar in both the groups (53.3 vs. 53.6%) and hence individually not associated with any risk. However, this allele was found to act additively in the presence of MTHFR 677T allele as evidenced by 8.11-fold (95% CI: 2.84–22.92) risk associated with MTHFR 677CT+TT/1298AC+CC genotypes cumulatively. Conclusion MTHFR C677T is a risk factor, whereas MTRR A66G and SHMT C1420T polymorphisms reduce risk for autism. MTHFR A1298C acts additively in increasing the risk for autism.
This paper references
Cerebral folate deficiency with developmental delay, autism, and response to folinic acid
P. Moretti (2005)
Autism, an extreme challenge integrative medicine
PM Kidd (2002)
A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida.
A. Wilson (1999)
Autism as a strongly genetic disorder: evidence from a British twin study.
A. Bailey (1995)
Cytoplasmic Serine Hydroxymethyltransferase Mediates Competition between Folate-dependent Deoxyribonucleotide andS-Adenosylmethionine Biosyntheses*
Katherine L. Herbig (2002)
Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children.
Gilbert Lelord (1982)
Controversies in the Treatment of Autistic Children: Vitamin and Drug Therapy
B. Rimland (1988)
Polymorphisms of one-carbon-metabolizing genes and risk of breast cancer in a population-based study.
X. Xu (2007)
Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.
S. James (2004)
Homocysteine remethylation enzyme polymorphisms and increased risks for neural tube defects.
H. Zhu (2003)
Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects?
S. Heil (2001)
Genetic polymorphisms in folate and homocysteine metabolism as risk factors for DNA damage
N. Botto (2003)
The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations.
D. J. Gaughan (2001)
Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal
M. Waly (2004)
5-Formyltetrahydrofolate Regulates Homocysteine Remethylation in Human Neuroblastoma*
S. Girgis (1997)
A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A.
Y. Jiang (2004)
Prevalence of methylene tetrahydrofolate reductase (MTHFR) gene polymorphism in South India
A Radha Rama Devi (2004)
Human methionine synthase reductase is a molecular chaperone for human methionine synthase.
K. Yamada (2006)
A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism.
D. Geier (2004)
A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
N. V. D. van der Put (1998)
Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine.
Robert A. Schatz (1981)
The knowledge base.
J. Akinsanya (1981)
Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase
K. Yamada (2001)
Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.
S. James (2006)
Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia.
C. Skibola (2002)
Worldwide distribution of a common methylenetetrahydrofolate reductase mutation.
J. A. Schneider (1998)
Polymorphisms of key enzymes in homocysteine metabolism affect diet responsiveness of plasma homocysteine in healthy women.
M. Silaste (2001)
Association of MTHFR Gene Variants with Autism
M. Boris (2004)
A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase
P. Frosst (1995)
Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base.
P. Kidd (2002)
Prevalence of methylene tetrahydrofolate reductase polymorphism in South Indian population
A. Radha (2004)
Biological effects of inhibitors of S-adenosylhomocysteine hydrolase.
P. Chiang (1998)
Relationship between methionine synthase, methionine synthase reductase genetic polymorphisms and deep vein thrombosis among South Indians
S. Naushad (2008)
Etiology of autism: genetic influences. Pediatrics 87:767–773
SE Folstein (1991)
Combined vitamin B6-magnesium treatment in autism spectrum disorder.
C. Nye (2002)
Etiology of autism: genetic influences.
S. Folstein (1991)
Increase in Plasma Homocysteine Associated with Parallel Increases in Plasma S-Adenosylhomocysteine and Lymphocyte DNA Hypomethylation*
P. Yi (2000)
This paper is referenced by
Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community
Arwa H Arab (2019)
Andhra Pradesh Journal of Psychological Medicine Ips-ap Chapter Executive Council Members Original Articles Delay in First Psychiatric Consultation and Its Reasons
Rajshekhar Bipeta (2012)
EPIGENETIC PROGRAMMING AND FETAL GROWTH RESTRICTIONS
José Carlos Ferreira (2010)
Evaluation of MTHFR Genetic Polymorphism as a Risk Factor in EgyptianAutistic Children and Mothers
Nagwa Abdel Meguid (2015)
MTRR A66G como um fator de risco para transtornos do espectro autista em uma amostra do sul do Brasil
Bibiane Armiliato de Godoy (2010)
Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder
Richard Eugene Frye (2014)
Achieving Optimal Outcomes in Autism: Treating Potentially Reversible Conditions Associated with Autism Spectrum Disorder
Richard Eugene Frye (2014)
Association of thymidylate synthase 5'-UTR 28bp tandem repeat and serine hydroxymethyltransfarase C1420T polymorphisms with susceptibility to acute leukemia.
Nageswara Rao Dunna (2014)
No association between MTHFR C677T polymorphism and completed suicide.
Izabela Chojnicka (2012)
A comprehensive meta-analysis of common genetic variants in autism spectrum conditions
Varun Warrier (2015)
Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
Olga Egorova (2020)
Analysis of methionine synthase (rs1805087) gene polymorphism in autism patients in Northern Iran.
Rosa Haghiri (2016)
Nasser Attia Elhawary (2019)
Effects of Febuxostat on Autistic Behaviors and Computational Investigations of Diffusion and Pharmacokinetics
Jamelle Simmons (2019)
Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: Systematic review and meta-analysis
Bahman Razi (2020)
Increased susceptibility to mild neonatal stress in MTHFR deficient mice
N. Kezurer (2013)
The plausibility of a role for mercury in the etiology of autism: a cellular perspective
Matthew Garrecht (2011)
Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation
D. Howsmon (2017)
Prioritization of Disease Susceptibility Genes Using LSM/SVD
Lejun Gong (2013)
Evaluation of C677T Polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) Gene in various Neurological Disorders
Sireesha Divyakolu (2013)
Association Study of Polymorphisms in Genes Relevant to Vitamin B12 and Folate Metabolism with Childhood Autism Spectrum Disorder in a Han Chinese Population
Zengyu Zhang (2018)
Increased Vulnerability to Oxidative Stress and Mitochondrial Dysfunction in Autism
Abha Chauhan (2015)
Autism Spectrum Disorder: 70 Years on and the Plot Thickens
Usha S. Naik (2015)
Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes
Richard Eugene Frye (2016)
The Molecular Basis of Autism
S Hossein Fatemi (2015)
Association of seven functional polymorphisms of one-carbon metabolic pathway with total plasma homocysteine levels and susceptibility to Parkinson's disease among South Indians
Nadella Kumudini (2014)
The complex genetics in autism spectrum disorders
Rui Hua (2015)
A study of MTRR 66 A > G gene polymorphism in patients with autism from northern Iran
Samereh Ajabi (2017)
Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder
Richard Eugene Frye (2015)
Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis.
Tahereh Sadeghiyeh (2019)
The genetics of autism and related traits
Varun Warrier (2018)
Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability
Samikshan Dutta (2011)See more