LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease

Abstract Background The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the ris...

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Main Authors: Aroma Agape Gopalai, Jia Lun Lim, Hui‐Hua Li, Yi Zhao, Thien Thien Lim, Gaik B. Eow, Santhi Puvanarajah, Shanthi Viswanathan, Mohamed Ibrahim Norlinah, Zariah Abdul Aziz, Soo Kun Lim, Chong Tin Tan, Ai Huey Tan, Shen‐Yang Lim, Eng‐King Tan, Azlina Ahmad Annuar
Format: Article
Language:English
Published: Wiley 2019-11-01
Series:Molecular Genetics & Genomic Medicine
Subjects:
Online Access:https://doi.org/10.1002/mgg3.604
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spelling doaj-2cdb4bd6a8f34f8a95f5ee225dbb99a22020-11-25T01:57:14ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-11-01711n/an/a10.1002/mgg3.604LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's diseaseAroma Agape Gopalai0Jia Lun Lim1Hui‐Hua Li2Yi Zhao3Thien Thien Lim4Gaik B. Eow5Santhi Puvanarajah6Shanthi Viswanathan7Mohamed Ibrahim Norlinah8Zariah Abdul Aziz9Soo Kun Lim10Chong Tin Tan11Ai Huey Tan12Shen‐Yang Lim13Eng‐King Tan14Azlina Ahmad Annuar15Faculty of Medicine, Department of Biomedical Science University of Malaya Kuala Lumpur MalaysiaFaculty of Medicine, Department of Biomedical Science University of Malaya Kuala Lumpur MalaysiaHealth Services Research Singapore General Hospital Singapore SingaporeDepartment of Clinical Translational Research Singapore General Hospital Singapore SingaporeIsland Hospital George Town MalaysiaDepartment of Neurology Hospital Pulau Pinang Penang MalaysiaDepartment of Neurology Hospital Kuala Lumpur Kuala Lumpur MalaysiaDepartment of Neurology Hospital Kuala Lumpur Kuala Lumpur MalaysiaHospital University Kebangsaan Malaysia Kuala Lumpur MalaysiaDepartment of Medicine Hospital Sultanah Nur Zahirah Kuala Terengganu MalaysiaFaculty of Medicine, Department of Medicine University of Malaya Kuala Lumpur MalaysiaFaculty of Medicine, Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders University of Malaya Kuala Lumpur MalaysiaFaculty of Medicine, Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders University of Malaya Kuala Lumpur MalaysiaFaculty of Medicine, Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders University of Malaya Kuala Lumpur MalaysiaDepartment of Neurology Singapore General Hospital Singapore SingaporeFaculty of Medicine, Department of Biomedical Science University of Malaya Kuala Lumpur MalaysiaAbstract Background The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K‐R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population. Methods Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age‐ and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay. Results A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta‐analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H. Conclusion This study reports that the N551K‐R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.https://doi.org/10.1002/mgg3.604LRRK2N551KParkinson's diseaseR1398H
collection DOAJ
language English
format Article
sources DOAJ
author Aroma Agape Gopalai
Jia Lun Lim
Hui‐Hua Li
Yi Zhao
Thien Thien Lim
Gaik B. Eow
Santhi Puvanarajah
Shanthi Viswanathan
Mohamed Ibrahim Norlinah
Zariah Abdul Aziz
Soo Kun Lim
Chong Tin Tan
Ai Huey Tan
Shen‐Yang Lim
Eng‐King Tan
Azlina Ahmad Annuar
spellingShingle Aroma Agape Gopalai
Jia Lun Lim
Hui‐Hua Li
Yi Zhao
Thien Thien Lim
Gaik B. Eow
Santhi Puvanarajah
Shanthi Viswanathan
Mohamed Ibrahim Norlinah
Zariah Abdul Aziz
Soo Kun Lim
Chong Tin Tan
Ai Huey Tan
Shen‐Yang Lim
Eng‐King Tan
Azlina Ahmad Annuar
LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
Molecular Genetics & Genomic Medicine
LRRK2
N551K
Parkinson's disease
R1398H
author_facet Aroma Agape Gopalai
Jia Lun Lim
Hui‐Hua Li
Yi Zhao
Thien Thien Lim
Gaik B. Eow
Santhi Puvanarajah
Shanthi Viswanathan
Mohamed Ibrahim Norlinah
Zariah Abdul Aziz
Soo Kun Lim
Chong Tin Tan
Ai Huey Tan
Shen‐Yang Lim
Eng‐King Tan
Azlina Ahmad Annuar
author_sort Aroma Agape Gopalai
title LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title_short LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title_full LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title_fullStr LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title_full_unstemmed LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title_sort lrrk2 n551k and r1398h variants are protective in malays and chinese in malaysia: a case–control association study for parkinson's disease
publisher Wiley
series Molecular Genetics & Genomic Medicine
issn 2324-9269
publishDate 2019-11-01
description Abstract Background The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K‐R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population. Methods Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age‐ and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay. Results A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta‐analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H. Conclusion This study reports that the N551K‐R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.
topic LRRK2
N551K
Parkinson's disease
R1398H
url https://doi.org/10.1002/mgg3.604
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