Glucocerebrosidase genetic variants in Malays with early and late-onset Parkinson’s disease
- Author:
Nur Fadhlina Mohamad Pakarulrazy
;
Saiful Effendi Syafruddin
;
Nurul Syakima Ab Mutalib
;
Azlina Ahmad Annuar
;
Shen-Yang Lim
;
Rahman Jamal
;
Nor Azian Abdul Murad
;
Norlinah Mohamed Ibrahim
- Publication Type:Journal Article
- Keywords:
Glucocerebrosidase;
Malay;
Parkinson’s disease (PD);
EOPD, LOPD
- From:Neurology Asia
2020;25(1):39-46
- CountryMalaysia
- Language:English
-
Abstract:
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 wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM 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.
- Full text:7.2020my0006.pdf
