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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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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