Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry
Mario Cornejo-Olivas1,2, Luis Torres3,4, Mario R. Velit-Salazar1,5, Miguel Inca-Martinez1, Pilar Mazzetti1,4, Carlos Cosentino3,4,Federico Micheli6, Claudia Perandones6, Elena Dieguez7, Victor Raggio8, Vitor Tumas9, Vanderci Borges10, Henrique B. Ferraz10,Carlos R. M. Rieder11, Artur Shumacher-Schuh11, Carlos Velez-Pardo12, Marlene Jimenez-Del-Rio12, Francisco Lopera12,Jorge Chang-Castello13, Brennie Andreé-Munoz14, Sarah Waldherr15,16, Dora Yearout15,16, Cyrus P. Zabetian15,16and Ignacio F. Mata15,16
1Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;2Northern Pacific Global Health Research Training Consortium, Bethesda, MD, USA;3Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;4Universidad Nacional Mayor de San Marcos, Lima, Peru;5Universidad Peruana CayetanoHeredia, Lima, Peru;6Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina;7Neurology Institute, Universidad de la Republica,Montevideo, Uruguay;8Department of Genetics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay;9Ribeirão Preto Medical School, Universidade de SãoPaulo, Ribeirão Preto, Brazil;10Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, SP, Brazil;11Hospital deClínicas de Porto Alegre, Porto Alegre, Brazil;12Neruroscience Research Group, Medical Research Institute, Universidad de Antioquia, Medellin, Colombia;13Department ofGenetics, School of Medici ne, Universidad de Guayaquil, Hospital Luis Vernaza, Guayaquil, Ecuador;14Service of Neurology, Hospital Luis Vernaza, Guayaquil, Ecuador;15VeteransAffairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA and16Department of Neurology, University of Washington, Seattle, WA, USACorrespondence: Ignacio F . Mata (nachofm@uw.edu)
Mutations in Leucine Repeat Rich Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson’s disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson’s disease, but this finding requires replication. We screened1734 Parkinson’s disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson’s disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson’s disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson’s disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common.
npj Parkinson’s Disease (2017) 3:19 ; doi:10.1038/s41531-017-0020-6
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