title: Lrrk2 p.Q1111H substitution and Parkinson's disease in Latin America.
abstract: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, with frequencies displaying a high degree of population-specificity. Although more than 100 coding substitutions have been identified, only seven have been proven to be highly penetrant pathogenic mutations. Studies however are lacking in non-white populations. Recently, Lrrk2 p.Q1111H (rs78365431) was identified in two affected Hispanic brothers and absent in 386 non-Hispanic white healthy controls. We therefore screened this variant in 1460 individuals (1150 PD patients and 310 healthy controls) from 4 Latin American countries (Peru, Chile, Uruguay and Argentina). In our case-control series from Peru and Chile we observed an increased frequency of Lrrk2 p.Q1111H in patients (7.9%) compared to controls (5.4%) although the difference did not reach significance (OR 1.38; p = 0.10). In addition, the frequency of Lrrk2 p.Q1111H varied greatly between populations and further screening in a set of pure Amerindian and pure Spanish controls suggested that this variant likely originated in an Amerindian population. Further studies in other Latin American populations are warranted to assess its role as a risk factor for Parkinson's disease. Screening in Parkinson's disease patients from under-represented populations will increase our understanding of the role of LRRK2 variants in disease risk worldwide.
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. nachofm@u.washington.edu
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Greggory J
authors.initials: GJ
authors.lastname: Wilhoite
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bacon
authors.forename: Mario
authors.initials: M
authors.lastname: Cornejo-Olivas
authors.forename: Pilar
authors.initials: P
authors.lastname: Mazzetti
authors.forename: Victoria
authors.initials: V
authors.lastname: Marca
authors.forename: Olimpio
authors.initials: O
authors.lastname: Ortega
authors.forename: Oscar
authors.initials: O
authors.lastname: Acosta
authors.forename: Carlos
authors.initials: C
authors.lastname: Cosentino
authors.forename: Luis
authors.initials: L
authors.lastname: Torres
authors.forename: Angel C
authors.initials: AC
authors.lastname: Medina
authors.forename: Carolina
authors.initials: C
authors.lastname: Perez-Pastene
authors.forename: Fernando
authors.initials: F
authors.lastname: Díaz-Grez
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Pablo
authors.initials: P
authors.lastname: Venegas
authors.forename: Marcelo
authors.initials: M
authors.lastname: Miranda
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Trujillo-Godoy
authors.forename: Luis
authors.initials: L
authors.lastname: Layson
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Avello
authors.forename: Elena
authors.initials: E
authors.lastname: Dieguez
authors.forename: Victor
authors.initials: V
authors.lastname: Raggio
authors.forename: Federico
authors.initials: F
authors.lastname: Micheli
authors.forename: Claudia
authors.initials: C
authors.lastname: Perandones
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Juan
authors.initials: J
authors.lastname: Segura-Aguilar
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005973:Glutamine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D007199:Indians, South American / Q000208:ethnology / Q000235:genetics; D007843:Latin America / Q000453:epidemiology / Q000208:ethnology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: D005973:Glutamine; D006639:Histidine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases