Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism status does not predict serum folate and B12 in children with Attention-Deficit/Hyperactivity Disorder (ADHD) (P5.6-042)

Objective: To contrast serum folate and B12 levels among MTHFR C677T polymorphisms in a cohort of children with ADHD. Background: Polymorphisms in the methylenetetrahydrofolate reductase enzyme (MTHFR), which allows for the metabolism of homocysteine to methionine, have been extensively investigated for a contributing role in a variety of neurologic diseases, including ADHD. The homozygous C677T (TT) polymorphism has been correlated with serum folate and B12 deficiency, which has been hypothesized to contribute to disease pathogenesis. Furthermore, several studies of healthy populations found that TT status was associated with decreased folate levels despite adequate folate intake. As such, TT status is often used as a rationale to treat patients with folate and B12 supplementation. Design/Methods: Serum folate and B12 levels as well as MTHFR C677T gene status (wild type (CC), heterozygous (CT), or homozygous (TT) polymorphism) were determined for 45 children with ADHD. ANOVA was used to contrast serum folate and B12 levels among MTHFR C677T genotypes. Results: Neither serum vitamin B12 [F2,42 = 0.46; p=0.63; n= (CC 14; CT 20; TT 11)] nor folate levels [F2,24 = 2.72; p=0.09; n= (CC 9; CT 12; TT 6)] were significantly different among MTHFR genotypes. Conclusions: The association of ADHD with C677T polymorphisms is controversial and as yet unsettled. Similarly, the role of vitamin B12 and folate have been debated. Our data suggest that the role of MTHFR C677T status in children with ADHD may not be directly coupled to vitamin B12 and folate levels. As such, further studies on the aforementioned questions should be careful to entertain the possibility that the MTHFR C677T gene status and vitamin B12 and folate levels are at least partially, if not entirely, independent. Disclosure: Dr. Silverstein has nothing to disclose. Dr. Junger has nothing to disclose. Dr. Pecor has nothing to disclose. Dr. Kornitzer has nothing to disclose.