Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry

• Published in: NPJ Parkinson's Disease Vol. 3; no. 1; pp. 19 - 6
• Main Authors: Cornejo-Olivas, Mario, Torres, Luis, Velit-Salazar, Mario R., Inca-Martinez, Miguel, Mazzetti, Pilar, Cosentino, Carlos, Micheli, Federico, Perandones, Claudia, Dieguez, Elena, Raggio, Victor, Tumas, Vitor, Borges, Vanderci, Ferraz, Henrique B., Rieder, Carlos R. M., Shumacher-Schuh, Artur, Velez-Pardo, Carlos, Jimenez-Del-Rio, Marlene, Lopera, Francisco, Chang-Castello, Jorge, Andreé-Munoz, Brennie, Waldherr, Sarah, Yearout, Dora, Zabetian, Cyrus P., Mata, Ignacio F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/1516; 692/617/375/1718; Biomedical and Life Sciences; Biomedicine; Genealogy; Mutation; Neurology; Neurosciences; Parkinson's disease; Latin America
• ISSN: 2373-8057; 2373-8057
• DOI: 10.1038/s41531-017-0020-6

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 screened 1734 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.
Genetic risk: Uncovering ethnic-specific mutations
A new study reveals the frequency of
Leucine-Rich Repeat Kinase 2
(
LRRK2
) mutations associated with Parkinson’s disease (PD) in Latin Americans. Ignacio F. Mata at the University of Washington and the VA Puget Sound Health Care System, Seattle, USA, and colleagues from six South American countries have screened the largest cohort of Latino PD patients ever assembled (1739) and 1104 healthy controls for
LRRK2
mutations that are known to cause PD in European-derived populations. They found that the p.G2019S missense mutation was the most common, although its frequency varied greatly between countries and was directly correlated with European ancestry. In contrast, the p.R1441G mutation which is common in Spain is rare in Latin America. Further analyses of this cohort will help to further characterize the genetic profile of PD patients in Latin America and contribute to the development of personalized medicines.