Polymorphism of HD and UCHL-1 genes in Huntington's disease

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.