Genetic Polymorphism of Methylenetetrahydrofolate Reductase in Children with Autism in Northeast China

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
2:00 PM
K. Wu1, L. Xia2, D. Zhao1, W. Xia1 and L. J. Wu1, (1)Harbin Medical University, Harbin, China, (2)The First Hospital of Harbin Medical University, Harbin, China
Background:  5, 10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Autism is a severe neurodevelopmental disorder which has intricate pathobiology with indispensable influences of genetic factors in the development. Although several autism genetic risk genes have been identified, the pathogenesis of autism is not fully explained.

Objectives:  This case-control study was undertaken to analyze the association between MTHFR C677T and A1298C polymorphisms and autism susceptibility in children of northeast China.

Methods:  A total of 263 cases (3-13 years-old; 237 boys and 26 girls) with autism and 70 controls (3-6 years-old; 59 boys and 11 girls) were randomly selected from the northeast areas of China. Analysis of the polymorphisms was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by direct sequencing.

Results:  

The C677T mutation (CT or TT genotype) and A1298C mutation (AC or CC genotype) were confirmed by sequencing. And the CT + TT genotype of C677T was present in 52.85% of autistic children and in 14.29% of nonautistic children (OR=6.726,95% CI 3.30-13.70, P<0.005). The frequencies of MTHFR A1298C mutant genotypes (27.76 vs. 12.86%) were found to be higher in autistic group compared with nonautistic group with 2.604-fold increased risk for autism (95% CI 1.23-5.51, P<0.005). When the individuals were classified according to MTHFR genotypes as follows: individuals with mutant C677T and mutant A1298C; individuals with mutant C677T and wild-type A1298C; individuals with wild-type C677T and mutant A1298C; individuals with wild-type C677T and wild-type A1298C, gene combination analysis showed a significant statistic difference (P<0.05).

Conclusions:  

These findings indicate that the polymorphisms of MTHFR C677T and A1298C genes may be a risk factor for autism in children of northeast China.

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