title: Examination of tetrahydrobiopterin pathway genes in autism.
abstract: Autism is a complex disorder with a high degree of heritability and significant phenotypic and genotypic heterogeneity. Although candidate gene studies and genome-wide screens have failed to identify major causal loci associated with autism, numerous studies have proposed association with several variations in genes in the dopaminergic and serotonergic pathways. Because tetrahydrobiopterin (BH4) is the essential cofactor in the synthesis of these two neurotransmitters, we genotyped 25 SNPs in nine genes of the BH4 pathway in a total of 403 families. Significant nominal association was detected in the gene for 6-pyruvoyl-tetrahydropterin synthase, PTS (chromosome 11), with P = 0.009; this result was not restricted to an affected male-only subset. Multilocus interaction was detected in the BH4 pathway alone, but not across the serotonin, dopamine and BH4 pathways.
authors.affiliation: Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Schnetz-Boutaud
authors.forename: B M
authors.initials: BM
authors.lastname: Anderson
authors.forename: K D
authors.initials: KD
authors.lastname: Brown
authors.forename: H H
authors.initials: HH
authors.lastname: Wright
authors.forename: R K
authors.initials: RK
authors.lastname: Abramson
authors.forename: M L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: J R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D001708:Biopterins; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin
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