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. 2019 Jun:63:204-208.
doi: 10.1016/j.parkreldis.2019.01.030. Epub 2019 Feb 4.

The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru

Carlos Velez-Pardo  1 , Oswaldo Lorenzo-Betancor  2 , Marlene Jimenez-Del-Rio  3 , Sonia Moreno  4 , Francisco Lopera  4 , Mario Cornejo-Olivas  5 , Luis Torres  6 , Miguel Inca-Martinez  7 , Pilar Mazzetti  8 , Carlos Cosentino  6 , Dora Yearout  2 , Sarah M Waldherr  2 , Cyrus P Zabetian  2 , Ignacio F Mata  9
Affiliations

The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru

Carlos Velez-Pardo et al. Parkinsonism Relat Disord. 2019 Jun.

Abstract

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.

Keywords: Colombia; GBA; Gaucher's disease; Genetics; Glucocerebrosidase; Parkinson's disease; Peru.

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Conflict of interest statement

DECLARATION OF INTEREST

The authors declare that they have no competing financial interests.

Figures

Figure 1.
Figure 1.. Pathogenic GBA mutation distribution in three different populations.
Frequency and distribution of GBA mutation carriers in PD patients from Colombia (A), Peru (B) and a US population [7] (C).
See this image and copyright information in PMC

References

    1. Deng H, Wang P, Jankovic J, The genetics of Parkinson disease, Ageing research reviews 42 (2018) 72–85. - PubMed
    1. Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Durr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG, Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease, N. Engl. J. Med 361(17) (2009) 1651–61. - PMC - PubMed
    1. Clark LN, Ross BM, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K, Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease, Neurology 69(12) (2007) 1270–7. - PMC - PubMed
    1. Chang D, Nalls MA, Hallgrimsdottir IB, Hunkapiller J, van der Brug M, Cai F, Kerchner GA, Ayalon G, Bingol B, Sheng M, Hinds D, Behrens TW, Singleton AB, Bhangale TR, Graham RR, A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci, Nat. Genet 49(10) (2017) 1511–1516. - PMC - PubMed
    1. Duran R, Mencacci NE, Angeli AV, Shoai M, Deas E, Houlden H, Mehta A, Hughes D, Cox TM, Deegan P, Schapira AH, Lees AJ, Limousin P, Jarman PR, Bhatia KP, Wood NW, Hardy J, Foltynie T, The glucocerobrosidase E326K variant predisposes to Parkinson’s disease, but does not cause Gaucher’s disease, Mov. Disord 28(2) (2013) 232–236. - PMC - PubMed

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