A Study of Potential Interactive Genetic Factors in Huntington's Disease

Aim: To assess the role of genetic factors, other than the CAG repeat length, on the development of Huntington's disease (HD) in an isolated Caucasian population in the south-west of Western Australia. Methods: 114 patients with symptomatic HD according to the Unified HD Rating Scale research criteria were examined along with 51 control patients. The length of the CAG repeat sequence in the IT15 gene and the adjacent CCG and Delta 2642 polymorphisms were determined by polymerase chain reaction along with common genotypes of the angiotensin-converting enzyme (ACE) and apolipoprotein E (APOE) genes. Results:The CAG expansion was associated with age of onset and the development of neurological dysfunction. We found no effect of the expanded CCG allele on age of onset, neurological dysfunction or the size of the CAG expansion. We observed a twofold increase in the Delta 2642 polymorphism and the risk of developing symptomatic HD which was not significant (OR 2.06; 95% CI 0.60-7.07). The presence of an APOE epsilon 4 allele was associated with an increased risk of HD which was not significant either (OR 1.04-1.73; 95% CI 0.10-10.68). ACE genotypes showed no association with risk factors for the disease. Conclusion: In our study of a geographically isolated Caucasian HD population in the south-west of Western Australia we have not observed that the expanded CCG allele, the A2642 polymorphism, the APOE EA allele and ACE genotypes are associated with an increased risk for the development of symptomatic HD. Copyright (c) 2006 S. Karger AG, Basel.