Abstract

Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of the polyglutamine (CAG) tract in the huntingtin (Htt) protein. The length of the CAG repeat is the main predictor of disease onset but only part of the variance is correlated with the age at onset (AAO). We therefore hypothesized that genetic modifiers should be enriched among Htt protein interactors. Recently we have indentified htt associated protein 1 (HAP-1) M441T polymorphism which modified the AAO of HD via reducing soluble htt degraded products and protecting against htt induced toxicity. To further explore potential genetic modifiers, we selected Duo as target. Duo is known as an interactor of HAP-1 and is important in synaptic maturation and dendritic spine dynamics. Four non-synonymous single nucleotide polymorphisms (SNPs) and one 5′ untranslated region (UTR) SNPs were chosen. They are located in exon 9, 12, 25 and 32, and regulatory element, respectively. We used the PCR restriction fragment length polymorphism method for screening. The results showed that 5′UTR had polymorphic frequency relevant to the database. We will enlarge the sample number and cross analyse the correlation between AAO, HAP-1 and Duo.