학술논문
Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients
Document Type
Report
Author
Source
The Pharmacogenomics Journal. June 1, 2014, Vol. 14 Issue 3, p289, 6 p.
Subject
Language
English
ISSN
1470-269X
Abstract
INTRODUCTION Idiopathic Parkinson's disease (PD) affects 1-3% of people older than 65 years, and its core symptoms are slowness of movements, rigidity and resting tremor. (1) The complete pathological pathway [...]
Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER! gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR) = 0.615, 95% confidence interval (CI) 0.426-0.887, P = 0.009) and visual hallucinations (PR = 0.515, 95% CI 0.295-0.899, P = 0.020). Our data suggest that HOMER! rs4704559 G allele has a protective role for the development of levodopa adverse effects. The Pharmacogenomics Journal (2014) 14, 289-294; doi:10.1038/tpj.2013.37; published online 15 October 2013 Keywords: dyskinesia; homer1; levodopa; Parkinson's disease; pharmacogenetics; visual hallucinations.
Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER! gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR) = 0.615, 95% confidence interval (CI) 0.426-0.887, P = 0.009) and visual hallucinations (PR = 0.515, 95% CI 0.295-0.899, P = 0.020). Our data suggest that HOMER! rs4704559 G allele has a protective role for the development of levodopa adverse effects. The Pharmacogenomics Journal (2014) 14, 289-294; doi:10.1038/tpj.2013.37; published online 15 October 2013 Keywords: dyskinesia; homer1; levodopa; Parkinson's disease; pharmacogenetics; visual hallucinations.