Folate Pathway Genetic Polymorphisms are Related to Attention Disorders in Childhood Leukemia Survivors

Received 7 November 2006; received in revised form 24 April 2007; accepted 29 May 2007. published online 10 October 2007.

Objective

To test the hypothesis that 5,10-methylenetetrahydroreductase (MTHFR) polymorphisms can partially explain the individual variation in developing attention-deficit/hyperactivity disorder (ADHD) after acute lymphoblastic leukemia (ALL) therapy.

Study design

Parents of 48 survivors of childhood ALL completed a clinical diagnostic process to identify subtypes of ADHD. Genotyping was performed with peripheral blood DNA for MTHFR (C677T and A1298C) polymorphisms.

Results

Eleven of the 48 patients (22.9%) had scores consistent with the inattentive symptoms of ADHD. Patients with genotypes related to lower folate levels (11 out of 39; 39.2%) were more likely to have ADHD. The A1298C genotype appeared to be the predominant linkage to the inattentive symptoms, leading to a 7.4-fold increase in diagnosis, compared with a 1.3-fold increase for the C677T genotype. Age at diagnosis and sex were not associated with inattentiveness.

Conclusions

Preliminary data imply a strong relationship between MTHFR polymorphisms and the inattentive symptoms of ADHD in survivors of childhood ALL.

Abbreviations: ADHD, Attention-deficit/hyperactivity disorder, ALL, Acute lymphoblastic leukemia, CSI, Child Symptom Inventory, MTHFR, 5,10-methylenetetrahydroreductase, MTX, Methotrexate, PCR, Polymerase chain reaction

a Learning Support Center for Child Psychology, Texas Children’s Hospital, Houston, TX

b Department of Pediatrics, Baylor College of Medicine, Houston, TX

c Texas Children’s Cancer Center, Houston, TX

d Division of AIDS & Health and Behavior Research, National Institute of Mental Health, Rockville, MD

e Childhood Cancer Epidemiology and Prevention Center, Houston, TX.

Reprint requests: Kevin R. Krull, PhD, Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, 332 N. Lauderdale St, MS 735, Memphis, TN 38105-2794.

No author reports any conflict of interest associated with this study.

PII: S0022-3476(07)00551-3

doi:10.1016/j.jpeds.2007.05.047

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