Genetic and environmental findings in early-onset Parkinson's disease Brazilian patients.
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.
Aguiar
Patricia de Carvalho
Pde C
Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo-SP, Brazil. patriciamc@einstein.br
Lessa
Patricia Silva
PS
Godeiro
Clecio
C
Barsottini
Orlando
O
Felício
Andre Carvalho
AC
Borges
Vanderci
V
Silva
Sonia Maria de Azevedo
SM
Saba
Roberta Arb
RA
Ferraz
Henrique Ballalai
HB
Moreira-Filho
Carlos A
CA
Andrade
Luiz Augusto F
LA
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
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