title: Genetic and environmental findings in early-onset Parkinson's disease Brazilian patients.
abstract: Parkinson's disease (PD) etiology has been attributed both to genetic and environmental factors. In this study, we investigated Brazilian early-onset PD (EOPD) patients for mutations in PARK2 and PARK8, exposure to environmental factors and possible correlations between PARK2 polymorphisms, environmental exposure, and disease age of onset. We enrolled 72 EOPD index patients and 81 healthy volunteers. Both groups were investigated for environmental exposure. EOPD patients were screened for PARK2 and PARK8 mutations. PARK2 coding polymorphisms Ser167Asn and Val380Leu were investigated in both groups. Mutations were present in 18% of the patients and in 32% of those with a positive family history. PARK2 mutations represented 12.5% and PARK8 mutations accounted for 5.5% of the mutations. A novel PARK2 mutation (D53X) was identified in 2 patients. A positive correlation was found between EOPD and well water drinking. In patients exposed to well water, a later age of onset was observed for those who carried at least one PARK2 380Leu allele. PARK2 mutations have an important role in EOPD Brazilian patients and PARK8 might be the second most important disease causing gene in this group. Well water drinking exposure represents a risk factor for EOPD and the PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.
authors.affiliation: Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo-SP, Brazil. patriciamc@einstein.br
authors.forename: Patricia de Carvalho
authors.initials: Pde C
authors.lastname: Aguiar
authors.forename: Patricia Silva
authors.initials: PS
authors.lastname: Lessa
authors.forename: Clecio
authors.initials: C
authors.lastname: Godeiro
authors.forename: Orlando
authors.initials: O
authors.lastname: Barsottini
authors.forename: Andre Carvalho
authors.initials: AC
authors.lastname: Felício
authors.forename: Vanderci
authors.initials: V
authors.lastname: Borges
authors.forename: Sonia Maria de Azevedo
authors.initials: SM
authors.lastname: Silva
authors.forename: Roberta Arb
authors.initials: RA
authors.lastname: Saba
authors.forename: Henrique Ballalai
authors.initials: HB
authors.lastname: Ferraz
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Moreira-Filho
authors.forename: Luiz Augusto F
authors.initials: LA
authors.lastname: Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil / Q000453:epidemiology; D016009:Chi-Square Distribution; D002648:Child; D004252:DNA Mutational Analysis; D004777:Environment; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases