Glucocerebrosidase genetic variants in Malays with early and late-onset Parkinson’s disease

• Main Authors: Pakarulrazy, Nur Fadhlina Mohamad, Syafruddin, Saiful Effendi, Mutalib, Nurul Syakima Ab, Ahmad-Annuar, Azlina, Lim, Shen Yang, Jamal, Rahman, Abdul Murad, Nor Azian, Ibrahim, Norlinah M.
• Format: Article
• Published: ASEAN Neurological Association 2020
• Subjects: R Medicine
• Online Access: http://eprints.um.edu.my/25418/; https://www.neurology-asia.org/articles/neuroasia-2020-25(1)-039.pdf

Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients. Methods: EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control were recruited. The GBA exons of these patients were sequenced using the Ion Torrent PGM™ System. Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G, p.S146L, p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition, c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715]. Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might predict the increase susceptibility of Malays to develop PD at young age. These findings could add knowledge into the existing evidences linking genetic alterations in GBA and PD. © 2020, ASEAN Neurological Association. All rights reserved.