The association study of Lrrk2 R1628P and Parkinson’s Disease
Date Issued
2009
Date
2009
Author(s)
Lee, Mei-Ching
Abstract
Background and purpose- Parkinson’s disease(PD) is a neurodegenerative disease with the clinical manifestations of resting tremor, rigidity and bradykinesia. Pathologically, there is dopaminergic neurondegeneration in the substia nigra and Lewy body deposition in the cytoplasm of dying neurons. Physiologically, the dopamine deficincy causes the dysregulation of motor control in the basal gaglia and leads to clinical symptoms. The etiology of dopaminergic neuron death is still uncertain. Genetic mutations causing familial PD has been disclosed recently. There are 8 gene found related to PD. One of the most important gene naming LRRK2 caused autosomal dominant parkinsonism. Some of the polymorphism of this gene has been found to be risk factor related to the development of sporadic PD. We analyse LRRK2 R1628P in multicenter including Taiwan Singapore to see the effect on PD. ethods and material- Diagnosis of PD is accoding to UK PD Society Brain Bank Clinical Diagnostic Criteria of PD. We included 484 PD and 341 normal control. Everyone signed inform consent and National Taiwan University IRB approved the Trial. We extrated DNA and to perform polychain reaction(PCR). Then sequenced the PCR produtcs. Finally, I checked the position of 4883 to see G>C.esults- Our results show a unique LRRK2 R1628P polymorphism has assoication with PD development in Han Chinese living in Taiwan and Singapore. In our group, the carrier rate in PD(GC，CC)（6.6%）doublednormal control(3.2%）. The C allele frquency is 3.4% in PD and 1.6% in normal control. ( p-value=0.025，odds ratio為2.15). IN R1628P mutation PD, one people has family history, five people are young onset(< 50 years old), and twenty-six people are late onset(>50 years old)。Another medical center in Taiwan and in Singapore also showed higher frequency of C-allele（3.0% v.s 2.2%; 2.6%v.s 1.2%）.iscussion- LRRK2 R1628P is unique in Han Chinese(Taiwan and Singapore). It showed specific genetic evolutio. Now, it is not clear about the effect of R1628P on cell or animal model. If there is more evidence about the relationship of mutation and diseas, we can do more for PD such as therpy. R1628P increaed the risk of PD. We can design PD gene chip assoicted other found PD gene. Neuroimage such as trancranial image and functional image can detected preclinical stage. Comined gene and neuroimage, we can deinfene PD as early as possible, and give specific therapy to delay PD development.onclusion- LRRK2 R1628P is a risk factor of PD in Han Chinese. Associated neuroimage, we can use in genetic conseling.
Subjects
Parkinson’s disease
gene
genetic conseling
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