title: Polymorphism of HD and UCHL-1 genes in Huntington's disease.
abstract: This study analyzed the association between the polymorphism of the Huntington's disease (HD) and ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) genes and the age of HD onset. We examined the size of trinucleotide CAG repeats in the HD gene of 53 individuals from families with a history of HD, six unrelated HD patients, and 51 healthy controls. Polymerase chain reaction and restriction fragment length polymorphism was performed to examine UCHL-1 S18Y polymorphism prevalence in this group. We identified five HD patients in the families and four pre-clinical HD patients in their high-risk offspring. The differences in S18Y allele prevalence between families and healthy controls were not statistically significant. The SY genotype was identified most frequently (prevalence >50%). The YY genotype was not identified in non-related HD patients, and the SS genotype had a higher prevalence than the SY genotype. The S allele was identified more frequently than the Y allele, and the difference with healthy controls was significant. Multiple linear regression analysis revealed that UCHL-1 S18Y polymorphism accounted for 15.6% of variance in the age of disease onset among 11 patients. The number of CAG repeats accounted for 71.4% of the variance. The size of CAG repeats in the HD gene is an important factor affecting the age at disease onset, but is not the only factor. UCHL-1 S18Y polymorphism is a modifier of HD with a modest regulatory role in the age at disease onset, suggesting that UCHL-1 may be involved in HD pathogenesis.
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China. xuerhe@163.com
authors.forename: Er-he
authors.initials: EH
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Jia
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D016009:Chi-Square Distribution; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012694:Serine / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014443:Tyrosine / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D055815:Young Adult
chemical_list: C482860:UCHL1 protein, human; D014443:Tyrosine; D012694:Serine; D043222:Ubiquitin Thiolesterase