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

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 dev...

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Autores principales: Gopalai, Aroma Agape, Lim, Jia Lun, Li, Hui‐Hua, Zhao, Yi, Lim, Thien Thien, Eow, Gaik B., Puvanarajah, Santhi, Viswanathan, Shanthi, Norlinah, Mohamed Ibrahim, Abdul Aziz, Zariah, Lim, Soo Kun, Tan, Chong Tin, Tan, Ai Huey, Lim, Shen‐Yang, Tan, Eng‐King, Ahmad Annuar, Azlina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825847/
https://www.ncbi.nlm.nih.gov/pubmed/31487119
http://dx.doi.org/10.1002/mgg3.604
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author Gopalai, Aroma Agape
Lim, Jia Lun
Li, Hui‐Hua
Zhao, Yi
Lim, Thien Thien
Eow, Gaik B.
Puvanarajah, Santhi
Viswanathan, Shanthi
Norlinah, Mohamed Ibrahim
Abdul Aziz, Zariah
Lim, Soo Kun
Tan, Chong Tin
Tan, Ai Huey
Lim, Shen‐Yang
Tan, Eng‐King
Ahmad Annuar, Azlina
author_facet Gopalai, Aroma Agape
Lim, Jia Lun
Li, Hui‐Hua
Zhao, Yi
Lim, Thien Thien
Eow, Gaik B.
Puvanarajah, Santhi
Viswanathan, Shanthi
Norlinah, Mohamed Ibrahim
Abdul Aziz, Zariah
Lim, Soo Kun
Tan, Chong Tin
Tan, Ai Huey
Lim, Shen‐Yang
Tan, Eng‐King
Ahmad Annuar, Azlina
author_sort Gopalai, Aroma Agape
collection PubMed
description 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.
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spelling pubmed-68258472019-11-07 LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease Gopalai, Aroma Agape Lim, Jia Lun Li, Hui‐Hua Zhao, Yi Lim, Thien Thien Eow, Gaik B. Puvanarajah, Santhi Viswanathan, Shanthi Norlinah, Mohamed Ibrahim Abdul Aziz, Zariah Lim, Soo Kun Tan, Chong Tin Tan, Ai Huey Lim, Shen‐Yang Tan, Eng‐King Ahmad Annuar, Azlina Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2019-09-05 /pmc/articles/PMC6825847/ /pubmed/31487119 http://dx.doi.org/10.1002/mgg3.604 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Gopalai, Aroma Agape
Lim, Jia Lun
Li, Hui‐Hua
Zhao, Yi
Lim, Thien Thien
Eow, Gaik B.
Puvanarajah, Santhi
Viswanathan, Shanthi
Norlinah, Mohamed Ibrahim
Abdul Aziz, Zariah
Lim, Soo Kun
Tan, Chong Tin
Tan, Ai Huey
Lim, Shen‐Yang
Tan, Eng‐King
Ahmad Annuar, Azlina
LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease
title 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_short 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
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825847/
https://www.ncbi.nlm.nih.gov/pubmed/31487119
http://dx.doi.org/10.1002/mgg3.604
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