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

Aroma Agape Gopalai, Jia Lun Lim, Hui Hua Li, Yi Zhao, Thien Thien Lim, Gaik B. Eow, Santhi Puvanarajah, Shanthi Viswanathan, Norlinah Mohamed Ibrahim, Zariah Abdul Aziz, Soo Kun Lim, Chong Tin Tan, Ai Huey Tan, Shen Yang Lim, Eng King Tan, Azlina Ahmad Annuar

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere604
JournalMolecular Genetics and Genomic Medicine
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Fingerprint

Malaysia
Parkinson Disease
Haplotypes
Mutation
Population
Nervous System Diseases
Genes
Single Nucleotide Polymorphism
Meta-Analysis
Brain

Keywords

  • LRRK2
  • N551K
  • Parkinson's disease
  • R1398H

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

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; Mohamed Ibrahim, Norlinah; Abdul Aziz, Zariah; Lim, Soo Kun; Tan, Chong Tin; Tan, Ai Huey; Lim, Shen Yang; Tan, Eng King; Ahmad Annuar, Azlina.

In: Molecular Genetics and Genomic Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Gopalai, AA, Lim, JL, Li, HH, Zhao, Y, Lim, TT, Eow, GB, Puvanarajah, S, Viswanathan, S, Mohamed Ibrahim, N, Abdul Aziz, Z, Lim, SK, Tan, CT, Tan, AH, Lim, SY, Tan, EK & Ahmad Annuar, A 2019, 'LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease', Molecular Genetics and Genomic Medicine. https://doi.org/10.1002/mgg3.604
Gopalai, Aroma Agape ; Lim, Jia Lun ; Li, Hui Hua ; Zhao, Yi ; Lim, Thien Thien ; Eow, Gaik B. ; Puvanarajah, Santhi ; Viswanathan, Shanthi ; Mohamed Ibrahim, Norlinah ; 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. In: Molecular Genetics and Genomic Medicine. 2019.
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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.",
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T2 - A case–control association study for Parkinson's disease

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AU - Lim, Jia Lun

AU - Li, Hui Hua

AU - Zhao, Yi

AU - Lim, Thien Thien

AU - Eow, Gaik B.

AU - Puvanarajah, Santhi

AU - Viswanathan, Shanthi

AU - Mohamed Ibrahim, Norlinah

AU - Abdul Aziz, Zariah

AU - Lim, Soo Kun

AU - Tan, Chong Tin

AU - Tan, Ai Huey

AU - Lim, Shen Yang

AU - Tan, Eng King

AU - Ahmad Annuar, Azlina

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