TY - JOUR
T1 - The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru
AU - Velez-Pardo, Carlos
AU - Lorenzo-Betancor, Oswaldo
AU - Jimenez-Del-Rio, Marlene
AU - Moreno, Sonia
AU - Lopera, Francisco
AU - Cornejo-Olivas, Mario
AU - Torres, Luis
AU - Inca-Martinez, Miguel
AU - Mazzetti, Pilar
AU - Cosentino, Carlos
AU - Yearout, Dora
AU - Waldherr, Sarah M.
AU - Zabetian, Cyrus P.
AU - Mata, Ignacio F.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - © 2019 Elsevier Ltd Background: Mutations in the glucocerebrosidase (GBA) gene are an important risk factor for Parkinson's disease (PD). However, most GBA genetic studies in PD have been performed in patients of European origin and very few data are available in other populations. Methods: We sequenced the entire GBA coding region in 602 PD patients and 319 controls from Colombia and Peru enrolled as part of the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD). Results: We observed a significantly higher proportion of GBA mutation carriers in patients compared to healthy controls (5.5% vs 1.6%; OR = 4.3, p = 0.004). Interestingly, the frequency of mutations in Colombian patients (9.9%) was more than two-fold greater than in Peruvian patients (4.2%) and other European-derived populations reported in the literature (4–5%). This was primarily due to the presence of a population-specific mutation (p.K198E) found only in the Colombian cohort. We also observed that the age at onset was significantly earlier in GBA carriers when compared to non-carriers (47.1 ± 14.2 y vs. 55.9 ± 14.2 y; p = 0.0004). Conclusion: These findings suggest that GBA mutations are strongly associated with PD risk and earlier age at onset in Peru and Colombia. The high frequency of GBA carriers among Colombian PD patients (∼10%) makes this population especially well-suited for novel therapeutic approaches that target GBA-related PD.
AB - © 2019 Elsevier Ltd Background: Mutations in the glucocerebrosidase (GBA) gene are an important risk factor for Parkinson's disease (PD). However, most GBA genetic studies in PD have been performed in patients of European origin and very few data are available in other populations. Methods: We sequenced the entire GBA coding region in 602 PD patients and 319 controls from Colombia and Peru enrolled as part of the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD). Results: We observed a significantly higher proportion of GBA mutation carriers in patients compared to healthy controls (5.5% vs 1.6%; OR = 4.3, p = 0.004). Interestingly, the frequency of mutations in Colombian patients (9.9%) was more than two-fold greater than in Peruvian patients (4.2%) and other European-derived populations reported in the literature (4–5%). This was primarily due to the presence of a population-specific mutation (p.K198E) found only in the Colombian cohort. We also observed that the age at onset was significantly earlier in GBA carriers when compared to non-carriers (47.1 ± 14.2 y vs. 55.9 ± 14.2 y; p = 0.0004). Conclusion: These findings suggest that GBA mutations are strongly associated with PD risk and earlier age at onset in Peru and Colombia. The high frequency of GBA carriers among Colombian PD patients (∼10%) makes this population especially well-suited for novel therapeutic approaches that target GBA-related PD.
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U2 - 10.1016/j.parkreldis.2019.01.030
DO - 10.1016/j.parkreldis.2019.01.030
M3 - Article
SN - 1353-8020
SP - 204
EP - 208
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -