Age at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1

作者：Taherzadeh Fard Elahe; Saft Carsten; Wieczorek Stefan; Epplen Joerg T; Arning Larissa^*

来源：Neurogenetics, 2010, 11(4): 435-439.

DOI：10.1007/s10048-010-0248-3

• Huntington disease
• Age at onset
• Modifier genes
• Polymorphism

In previous candidate gene studies, associations of the age at onset (AO) in Huntington disease (HD) have been reported with genetic variations in the genes encoding adenosinergic A(2A) receptor (ADORA2A), human huntingtin-associated protein-1 (HAP1) and the single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1). Here, we sought to replicate these associations in an established study population of 419 unrelated German HD patients. AO was defined as the age at which the first motor signs of HD appeared, motor AO (mAO). For 215 patients, also information about the first behavioural or cognitive signs of HD was available, so that we also tested for an association with the earliest AO. No association was found with OGG1. For HAP1, we found modest evidence for association with the same risk allele as in the original sample and mAO. Yet, we replicated the previously reported association between the original ADORA2A polymorphism when using the earliest AO. Additionally, we identified new associations in the same gene, thus further supporting the potential contribution of ADORA2A to the pathogenesis of HD.

• 出版日期2010-10