title: Mutational screening of PARKIN identified a 3' UTR variant (rs62637702) associated with Parkinson's disease.
abstract: PRKN mutations have been linked to Parkinson's disease (PD). Most of the mutational screenings have focused on the coding exons. The 3' untranslated region (UTR) could also harbor functionally relevant nucleotide changes. We performed a mutational screening of PRKN in a cohort of early-onset PD patients (n = 235) from Spain. We found 16 mutations (five new): 16 patients (7 %) carried two mutations and only one mutation was found in 28 (12 %). Patients with two mutations had significantly lower mean age (30 ± 9 years) compared to patients with one (40 ± 7) or no mutation (42 ± 7). We found a total of 15 nucleotide variants (three new) in the 3' UTR region. The frequency of carriers of the rare rs62637702 G allele (*94A/G) was significantly lower among the patients compared to healthy controls (n = 418) (0.03 vs. 0.004; p < 0.001), suggesting a protective role for this allele. In order to investigate the basal effect of this variant, we performed luciferase assays. No different basal activity was observed between the two alleles. In conclusion, the rs62637702 polymorphism was associated with PD. This could be a surrogate marker for disease risk, in linkage disequilibrium with other non-identified functional variant.
authors.affiliation: Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: de Mena
authors.forename: L Luís
authors.initials: LL
authors.lastname: Samaranch
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Lucía F
authors.initials: LF
authors.lastname: Cardo
authors.forename: René
authors.initials: R
authors.lastname: Ribacoba
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jaione
authors.initials: J
authors.lastname: Irigoyen
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Germán
authors.initials: G
authors.lastname: Moris
authors.forename: Manuel
authors.initials: M
authors.lastname: Menéndez
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Elena
authors.initials: E
authors.lastname: Lorenzo
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein