Beta-synuclein gene variants and Parkinson's disease: a preliminary case-control study.
Aggregation and fibrillization of the alpha-synuclein protein, which is the main component of Lewy bodies, may represent important processes in the pathogenesis of Parkinson's disease (PD). Several in vivo and in vitro studies suggest that beta-synuclein may be a natural negative regulator of alpha-synuclein aggregation and fibrillization. The goal of the present study was to investigate the association of two polymorphisms (rs35035889 and rs1352303) in the beta-synuclein (SNCB) gene with PD. Our case-control study included a total of 370 case-unaffected sibling pairs and 168 case-unrelated control pairs (538 pairs total). The subjects were recruited from an ongoing study of the molecular epidemiology of PD in the Upper Midwest (USA). We employed a liberalization of the sibling transmission disequilibrium test to study the main effects of the gene variants for subjects overall and for strata defined by age at study, gender, ethnicity, clinical diagnostic certainty, dementia, and family history of PD (adjusted for age at study and gender as appropriate). The analyses were conducted for each SNCB variant separately, and also for two-locus haplotypes using score tests. Neither of the SNCB SNPs examined were associated with PD overall or in strata, and haplotype analyses were negative as well. However, one of the two SNPs (rs1352303) was associated with a delayed age at onset of PD in women. The results of this preliminary study suggest that the SNCB locus, though not a susceptibility gene for PD, might modify the age at onset of PD.
Brighina
Laura
L
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Okubadejo
Njide U
NU
Schneider
Nicole K
NK
Lesnick
Timothy G
TG
de Andrade
Mariza
M
Cunningham
Julie M
JM
Farrer
Matthew J
MJ
Lincoln
Sarah J
SJ
Rocca
Walter A
WA
Maraganore
Demetrius M
DM
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D014481:United States / Q000453:epidemiology; D051846:beta-Synuclein / Q000235:genetics*
D051846:beta-Synuclein