E05 Age of onset of Huntington's disease is not modulated by HCAD R196K polymorphism

Abstract

Background The size of the CAG repeat tract is the major determinant of age of onset (AO) in Huntington9s disease (HD). However, the number of the CAG repeats does not allow accurate prediction of AO, only 30%–70% of the variance in AO can be explained by the repeat size alone. R196K polymorphism in the human caspase activated DNase (hCAD) gene is one of the strong candidate modifiers, since DNases are responsible for DNA degradation during apoptotic cell death. Aim We aimed to analyse the contribution of hCAD R196K polymorphism to the AO of Turkish HD patients. Methods The study population consists of 99 unrelated patients with the clinical diagnosis of HD. Genomic DNA samples were genotyped by PCR-RFLP analysis using AluI restriction enzyme. Genotype and allele frequencies were computed. The variability in AO attributable to the CAG repeat numbers and the genotypes were calculated by linear regression. Results It was shown that the CAG repeats explained 40.8% of the variance in AO. However, the genotypes did not explain the variance in AO (p=0.115) in the studied population. Conclusions An association between the hCAD R196K polymorphism and AO of Indian HD patients was recently reported. However, a following replication study could not confirm this result. The findings of this study also failed to replicate the original association. It is possible that an association can exist among Indians, or the results are due to chance or bias since the population size was relatively small. It will be wise to analyse various larger populations in order to draw a conclusion about the contribution of the hCAD gene in HD.