Aging Modifies the Effect of GCH1 RS11158026 on DAT Uptake and Parkinson's Disease Clinical Severity

• Published in: Neurobiology of aging 2017-02, Vol.50, p.39-46
• Main Authors: Webb, Joseph, B.S, Willette, Auriel A., Ph.D., M.S
• Format: Article
• Language: English
• Subjects: Age; Aged; Aging - physiology; Alleles; alpha-Synuclein - cerebrospinal fluid; DAT-SPECT; Disease Progression; Dopamine - metabolism; Executive Function; Female; GTP Cyclohydrolase - genetics; GTP Cyclohydrolase - physiology; Guanosine triphosphate cyclohydrolase-1 (GCH1); Humans; Internal Medicine; Male; Middle Aged; Neurology; Parkinson Disease - cerebrospinal fluid; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - psychology; Parkinson's disease; Parkinson's Progression Marker Initiative (PPMI); Polymorphism, Genetic; Severity of Illness Index
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2016.10.006

Abstract Novel single nucleotide polymorphisms within Parkinson’s disease (PD) can predict disease risk, but their influence on clinical, cognitive and neurobiological indices remain unexplored. We investigated differences between functional polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1 (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among newly diagnosed, untreated PD subjects and age-matched controls from the Parkinson's Progression Markers Initiative, T allele carriers showed higher PD risk (Odds Ratio=1.23, P=0.048), earlier age of onset by 5 years (P=0.003), and lower striatal DAT uptake (P=0.003). Carriers also had increased CSF α-synuclein (P=0.016), worse motor function (P=0.041), anxiety (P=0.038), and executive function (P