title: Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders.
abstract: The rationale of the current study was to test the clinical utility of the folate pathway genetic polymorphisms in predicting the risk for autism spectrum disorders (ASD) and to address the inconsistencies in the association of MTHFR C677T and hyperhomocysteinemia with ASD.
  
  
  
  An artificial neural network (ANN) model was developed from the data of 138 autistic and 138 nonautistic children using GCPII C1561T, SHMT1 C1420T, MTHFR C677T, MTR A2756G, and MTRR A66G as the predictors of autism risk. A neuro fuzzy model was developed to explore the genetic determinants of homocysteine. Meta-analyses were carried out on 1361 ASD children and 6591 nonautistic children to explore the association of MTHFR C677T and homocysteine with the risk for ASD.
  
  
  
  The ANN model showed 63.8% accuracy in predicting the risk of autism. Hyperhomocysteinemia was observed in autistic children (9.67±4.82 vs. 6.99±3.21 μmol/l). The neuro fuzzy model showed synergistic interactions between MTHFR C677T and MTRR A66G inflating homocysteine levels. The meta-analysis showed MTHFR to be a genetic risk factor for autism in both fixed-effects (odds ratio: 1.47, 95% confidence interval: 1.31-1.65) and random-effects (odds ratio: 1.57, 95% confidence interval: 1.16-2.11) models. The meta-analysis of nine studies showed hyperhomocysteinemia as a significant risk factor for autism in both fixed-effects (P<0.0001) and random-effects (P=0.026) models.
  
  
  
  Genetic polymorphisms of the folate pathway were moderate predictors of autism risk. MTHFR C677T and hyperhomocysteinemia have been identified as risk factors for autism worldwide. Synergistic interactions between MTHFR C677T and MTRR A66G increase homocysteine.
authors.affiliation: aBiochemical Genetics, Sandor Life Sciences Pvt Ltd bCenter for DNA Fingerprinting and Diagnostics cNiloufer Children's Hospital dRainbow Children's Hospital, Hyderabad eSchool of Chemical and Biotechnology, SASTRA University, Thanjavur, India fCenter of Excellence in Biotechnology Research gDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Naushad
authors.initials: N
authors.lastname: Shaik Mohammad
authors.forename: P
authors.initials: P
authors.lastname: Sai Shruti
authors.forename: Venkat
authors.initials: V
authors.lastname: Bharathi
authors.forename: Chintakindi
authors.initials: C
authors.lastname: Krishna Prasad
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
authors.forename: Usha
authors.initials: U
authors.lastname: Naik
authors.forename: Akella
authors.initials: A
authors.lastname: Radha Rama Devi
mesh_terms: D000483:Alleles; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006710:Homocysteine / Q000097:blood / Q000235:genetics; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)