A functional polymorphism of the GTP cyclohydrolase 1 gene predicts attention performance

Abstract

Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin, a cofactor for aromatic amino acid hydroxylases and nitric oxide synthases. As monoamine neurotransmitters are synthesized by the reactions catalyzed by tyrosine hydroxylase and tryptophan hydroxylase, alterations in the content of tetrahydrobiopterin affect the monoamine levels in the brain. Here, we examined the possible association of a functional single-nucleotide polymorphism (SNP) of the GCH1 gene, rs841 (C+243T), with attentional function as assessed by the Continuous Performance Test-Identical Pairs version (CPT-IP) in healthy individuals. We found that homozygous T/T genotype carriers of rs841 scored lower performance on the CPT-IP test. Our data suggest that alterations in GCH1 activity affect attentional function, especially sustained attention and vigilance.