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Genetic association study of LRRK2 exonic variants with susceptibility to Parkinson disease in Korean ethnicity

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Authors
엄관희
Advisor
전범석
Major
의과대학 의학과
Issue Date
2013-02
Publisher
서울대학교 대학원
Keywords
Parkinson diseaseLRRK2exonic variant
Description
학위논문 (석사)-- 서울대학교 대학원 : 의학과 뇌신경과학 전공, 2013. 2. 전범석.
Abstract
Introduction: The number of LRRK2 allelic variant has been reported more than one hundred thirty. Only a few representative allelic variants were studied in Korean ethnicity regarding the contribution of each variant to Parkinson disease (PD). Due to the ethnicity-specific distribution of variants, it is implausible to apply the results of studies conducted in other ethnicity to Korean ethnicity. Through sequencing 122 markers of LRRK2 we investigated the frequency and the susceptibility to PD of each allelic variant in Korean ethnicity.
Methods: A total of 1069 unrelated subjects consisting of 663 sporadic PD patients and 406 healthy controls were included. As we are a participant of GEO-PD (the genetic epidemiology of Parkinsons disease consortium) project, 122 markers of LRRK2 were genotyped. Pearsons chi-squared test was used to assess allelic association with PD. Then, we analyzed them through logistic regression analysis adjusting for age and sex to ascertain which markers modulate the risk of PD and to determine the extent to which the markers modulate the risk of PD.
Results: None of LRRK2 exonic variants showed statistically significant association with the risk of PD. Presumptively, LRRK2 p.N551K (rs7308720
OR 0.69, 95% CI 0.52-0.92
p=0.012), p.R1398H (rs7133914
OR 0.68, 95% CI 0.51-0.91
p=0.009), p.K1423K (rs11175964
OR 0.69, 95% CI 0.52-0.93
p=0.014), p.M2397T (rs3761863
OR 0.73, 95% CI 0.56-0.95
p=0.020) carriers showed lower risk of PD than non-carriers
LRRK2 p.A419V (rs34594498
OR 2.21, 95% CI 1.11-4.38
p=0.023) carriers presented higher risk of PD than non-carriers using dominant model-based logistic regression analysis. In linkage disequilibrium analysis, p.N551K, p.R1398H, p.K1423K were in strong LD together (r2>0.8).
Conclusions: In Korean population, presumptively, p.R1398H, p.N551K, p.K1423K variants constituting a haplotype modulate the risk of PD favorably, whereas p.A419V is associated with increased risk of PD. Although this result did not show statistically significant association, further study with sufficient number of subjects can confirm the result of this study.
Language
English
URI
https://hdl.handle.net/10371/132519
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Master's Degree_의학과)
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