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Aberrations in folate metabolic pathway and altered susceptibility to autism

Mohammad, Naushad Shaika; Jain, Jamal Md Nurula; Chintakindi, Krishna Prasada; Singh, Ram Prakasha; Naik, Ushab; Akella, Radha Rama Devia

doi: 10.1097/YPG.0b013e32832cebd2
Original Articles

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.

aCenter for DNA Fingerprinting and Diagnostics

bInstitute of Child Health, Niloufer Hospital, Hyderabad, India

Correspondence to Dr Radha Rama Devi Akella, MD, Consultant Medical Geneticist, Diagnostic Division, Center for DNA Fingerprinting and Diagnostics (CDFD) 7-18, Nacharam, Hyderabad-500076, Andhra Pradesh, India

Tel: +91 40 27171462; e-mail:

Received 27 May 2008 Revised 12 December 2008 Accepted 12 March 2009

© 2009 Lippincott Williams & Wilkins, Inc.