Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors.
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.


METHODS
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.
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology / Q000235:genetics*; D002648:Child; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+) / Q000187:drug effects / Q000235:genetics*; D010290:Parents; D011110:Polymorphism, Genetic / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D011795:Surveys and Questionnaires; D017741:Survivors
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+); D008727:Methotrexate