title: Folate metabolism gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with ADHD in myelomeningocele patients.
abstract: The objective of this study was to examine the relation between the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and behaviors related to attention- deficit/hyperactivity disorder (ADHD) in individuals with myelomeningocele. The rationale for the study was twofold: folate metabolizing genes, (e.g. MTHFR), are important not only in the etiology of neural tube defects but are also critical to cognitive function; and individuals with myelomeningocele have an elevated incidence of ADHD. Here, we tested 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder behavior using the Swanson Nolan Achenbach Pelham-IV ADHD rating scale. Myelomeningocele participants in this group for whom DNAs were available were genotyped for seven single nucleotide polymorphisms (SNPs) in the MTHFR gene. The SNPs were evaluated for an association with manifestation of the ADHD phenotype in children with myelomeningocele. The data show that 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD; of these 70.1% had scores consistent with the predominantly inattentive subtype. In addition, we also show a positive association between the SNP rs4846049 in the 3'-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants. These results lend further support to the finding that behavior related to ADHD is more prevalent in patients with myelomeningocele than in the general population. These data also indicate the potential importance of the MTHFR gene in the etiology of the ADHD phenotype.
authors.affiliation: Department of Pediatrics, University of Texas Medical School at Houston, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Spellicy
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
authors.forename: Jack M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Paul T
authors.initials: PT
authors.lastname: Cirino
authors.forename: Maureen
authors.initials: M
authors.lastname: Dennis
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Carla A
authors.initials: CA
authors.lastname: Martinez
authors.forename: Kit Sing
authors.initials: KS
authors.lastname: Au
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D001519:Behavior; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008591:Meningomyelocele / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)