title: Methyltetrahydrofolate reductase polymorphism influences onset of Huntington's disease.
abstract: Onset of Huntington's disease (HD) negatively correlates with CAG repeat length of the HD gene, which encodes the protein huntingtin. This protein interacts with the homocysteine metabolizing enzyme cystathionine betasynthase (CBS). Objective of this study was to analyze the impact of CAG repeats, polymorphisms of various homocysteine metabolizing enzymes, like CBS, Methyltetrahydrofolate Reductase (MTHTR), Methionine Synthase Reductase (MSR) and methionine synthase (MS) on HD onset in 171 patients. The significant impact of CAG repeats on HD onset (chi2= 25.54, FG = 4, p<0.0001) with a significant correlation between both (R= -0.521, p=0.01) was obvious. HD patients with the homozygous MTHFR-1298-CC significantly (p = 0.024) earlier experienced HD symptoms. There was no influence demonstrable of CBS, MSR and MS. Determination of MTHFR polymorphisms and CAG repeats enables screening for subjects with putative early HD onset in order to study neuroprotective compounds in their efficacy to delay HD symptoms.
authors.affiliation: Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Brune
authors.forename: J
authors.initials: J
authors.lastname: Andrich
authors.forename: M
authors.initials: M
authors.lastname: Gencik
authors.forename: C
authors.initials: C
authors.lastname: Saft
authors.forename: Th
authors.initials: T
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Valentin
authors.forename: H
authors.initials: H
authors.lastname: Przuntek
authors.forename: J T
authors.initials: JT
authors.lastname: Epplen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D018709:Statistics, Nonparametric; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)