Aberrations in folate metabolic pathway and altered susceptibility to autism.

Objective To investigate whether genetic polymorphismsare the underlying causes for aberrations in folate pathwaythat was reported in autistic children.Basic methods A total of 138 children diagnosed asautistic based on Diagnostic and Statistical Manualof Mental Disorders, fourth edition criteria and AutismBehavior Checklist scoring and 138 age and sex matchedchildren who are nonautistic were tested for five geneticpolymorphisms, that is, cytosolic serine hydroxyl methyltransferase (SHMT1 C1420T), methylene tetrahydrofolatereductase (MTHFR C677T and MTHFR A1298C),methionine synthase reductase (MTRR A66G),methionine synthase (MS A2756G) using PCR-restrictionfragment length polymorphism methods. Fisher exacttest and logistic regression analysis were used forstatistical analyses.Results MTHFR 677T-allele frequency was found tobe higher in autistic children compared with nonautisticchildren (16.3 vs. 6.5%) with 2.79-fold increased riskfor autism [95% confidence interval (CI): 1.58–4.93]. Thefrequencies of MTRR 66A allele (12.7 vs. 21.0%) and SHMT1420T allele (27.9 vs. 45.3%) were lower in autistic groupcompared 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-allelefrequency was similar in both the groups (53.3 vs.53.6%) and hence individually not associated withany risk. However, this allele was found to act additivelyin presence of MTHFR 677T allele as evidenced by8.11-fold (95% CI: 2.84–22.92) risk associated withMTHFR 677CT+TT/1298AC+CC genotypes cumulatively.Conclusion MTHFR C677T is a risk factor, whereasMTRR A66G and SHMT C1420T polymorphismsreduce risk for autism. MTHFR A1298C actsadditively in increasing the risk for autism. Psychiatr Genet00:000–000