Citation: Rai V and Kumar P. Methylenetetrahydrofolate Reductase A1298C Polymorphism and Autism Susceptibility. Austin J Autism & Relat Disabil. 2018; 4(1): 1048. Austin J Autism & Relat Disabil - Volume 4 Issue 1 - 2018 ISSN: 2472-341X | www.austinpublishinggroup.com Rai et al. © All rights are reserved Austin Journal of Autism & Related Disabilities Open Access Abstract Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate/homocysteine metabolism. A polymorphism A1298C has been reported to be linked with risk of several diseases/disorders like birth defects, metabolic and psychiatric disorders and different cancers. The association between autism and MTHFR gene A1298C polymorphism has been investigated in several case-control studies, which rendered contradictory results. Aim: To shed light on association between MTHFR A1298C polymorphism and risk of autism, a meta-analysis of published case control association studies was conducted. Methods: Four electronic databases: PubMed, Google Scholars, Elsevier and Springer Link were searched up to August, 2016. All statistical analyses were performed using MetaAnalyst and Mix (version 1.7). Odds ratios (ORs) with their 95% conidence intervals (95% CIs) were calculated. Total seven studies with 1,424 cases and 1,513 controls were included in the present meta- analysis. Results: The results of meta-analysis suggested that there were no signiicant association between A1298C polymorphism and autism risk using overall comparisons in ive genetic models (A vs C: OR=0.99, 95%CI=0.80- 1.23, p=0.005; AC vs AA: OR = 1.04, 95% CI = 0.75-1.43, p = 0.82; CC vs AA: OR = 0.16, 95% CI = 0.06-0.45, p = 0.006; CC+AC vs AA: OR = 0.45, 95% CI = 0.25-0.80, p = 0.006; CC vs AC+AA: OR = 0.15, 95% CI = 0.06-0.37, p<0.0001)). Publication bias was absent. Conclusion: In conclusion, results of present meta-analysis showed no signiicant association between MTHFR A1298C polymorphism and autism risk. Keywords: Autism; MTHFR; A1298C; Homocysteine here are several evidences that in autistic children, DNA methylation and DNA repair are altered [16,17] as well as dysregulation of redox homeostasis [18], which reinforces a critical role for CI metabolism in the etiology of ASDs [15]. One carbon metabolic pathway include several genes and most of them are polymorphic especially methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) and frequency of mutant alleles varies greatly worldwide [19-25]. Folate facilitates methionine synthesis from homocysteine by acting as a cofactor for methylene tetrahydrofolate reductase (MTHFR) which converts 5,10-methylenetetrahydrofolate (CH2THF) to 5-methyltetrahydrofolate (CH3THF). 5-methyltetrahydrofolate donates methyl group for the conversion of homocysteine in to methionine, which further converted in to S-adenosyl-methionine (SAM). SAM is universal methyl group donor, which transfer methyl to DNA, RNA, proteins, phospholipids, or neurotransmitters [26]. Consistently global DNA hypomethylation observed in autistic children [27-29]. Methyl deiciency may strongly impact epigenetic remodeling during key periods of development. MTHFR gene is 20 kb long (20,336 bp) and mapped at 1p36.3 Introduction Autism is a complex neurodevelopment disorder involving multiple organ systems, primarily immunological, gastrointestinal and neurological ones [1] and appears in the early years of life [2- 4]. It is currently estimated that 3-6 children out of 1000 worldwide have autism spectrum disorder (ASD) [5]. he incidence of autism has increased rapidly in recent decades [6,7]. It is a heterogeneous neurological disorder characterized by three core behavior abnormalities-namely, deicits in social interaction, reduced verbal and nonverbal communication, and highly focused stereotyped behaviors that emerge ater a period of relatively normal development [8]. A number of factors such as genetic, epigenetic, environmental and autoimmune function have been implicated in the etiology of autism [6,9-14]. One carbon (C1) metabolism is a likely pathway to regulate epigenetic processes in autism [15]. CI metabolism is comprised of three interconnected pathways-folate cycle, methionine cycle and transsulfuration cycle. he folate and methionine pathway mediates de novo nucelotide synthesis for DNA repair and replication and DNA methylations. he transsulfuration pathway balance cellular redox. Research Article Methylenetetrahydrofolate Reductase A1298C Polymorphism and Autism Susceptibility Rai V* and Kumar P Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, India *Corresponding author: Vandana Rai, Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur- 222 003, India Received: March 22, 2018; Accepted: May 09, 2018; Published: May 16, 2018