TY - JOUR
T1 - α-Synuclein, alcohol use disorders, and Parkinson disease
T2 - A case-control study
AU - Brighina, Laura
AU - Schneider, Nicole K.
AU - Lesnick, Timothy G.
AU - de Andrade, Mariza
AU - Cunningham, Julie M.
AU - Mrazek, David
AU - Rocca, Walter A.
AU - Maraganore, Demetrius M.
N1 - Funding Information:
Funding was provided by grants NS33978 and ES10751 (National Institutes of Health).
PY - 2009/7
Y1 - 2009/7
N2 - Collaborative pooled analyses demonstrated that allele length variability of the dinucleotide repeat sequence within the α-synuclein gene promoter (SNCA REP1) is associated with Parkinson disease (PD) worldwide. Other studies demonstrated that variability in the SNCA promoter is also associated with alcohol use disorders, but not consistently. Yet other studies demonstrated that alcohol use disorders are inversely associated with PD, but not consistently. The aim of this study was to clarify the patterns of association between REP1 genotype, alcohol use disorders, and PD. Cases were recruited from the Department of Neurology of the Mayo Clinic in Rochester, MN. The controls included unaffected siblings and unrelated controls. We assessed alcohol use via a structured telephone interview and screened for alcohol use disorders using the CAGE questionnaire. REP1 genotyping was performed using an ABI 3730XL platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression models. We recruited 893 case-control pairs. There was an increasing risk of PD with increasing SNCA REP1 allele length (OR 1.18 for each REP1 genotype score unit, 95% CI 1.02-1.35; p = 0.02). There was a decreasing risk of PD with increasing CAGE score (p = 0.01). The association of REP1 score with PD remained significant after adjusting for CAGE score, and the association of CAGE score with PD remained significant after adjusting for REP1 score. There were no pairwise interactions. Our findings suggest that SNCA REP1 genotype and alcohol use disorders are independently associated with PD.
AB - Collaborative pooled analyses demonstrated that allele length variability of the dinucleotide repeat sequence within the α-synuclein gene promoter (SNCA REP1) is associated with Parkinson disease (PD) worldwide. Other studies demonstrated that variability in the SNCA promoter is also associated with alcohol use disorders, but not consistently. Yet other studies demonstrated that alcohol use disorders are inversely associated with PD, but not consistently. The aim of this study was to clarify the patterns of association between REP1 genotype, alcohol use disorders, and PD. Cases were recruited from the Department of Neurology of the Mayo Clinic in Rochester, MN. The controls included unaffected siblings and unrelated controls. We assessed alcohol use via a structured telephone interview and screened for alcohol use disorders using the CAGE questionnaire. REP1 genotyping was performed using an ABI 3730XL platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression models. We recruited 893 case-control pairs. There was an increasing risk of PD with increasing SNCA REP1 allele length (OR 1.18 for each REP1 genotype score unit, 95% CI 1.02-1.35; p = 0.02). There was a decreasing risk of PD with increasing CAGE score (p = 0.01). The association of REP1 score with PD remained significant after adjusting for CAGE score, and the association of CAGE score with PD remained significant after adjusting for REP1 score. There were no pairwise interactions. Our findings suggest that SNCA REP1 genotype and alcohol use disorders are independently associated with PD.
KW - Alcohol use disorders
KW - Parkinson disease
KW - α-Synuclein
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U2 - 10.1016/j.parkreldis.2008.11.011
DO - 10.1016/j.parkreldis.2008.11.011
M3 - Article
C2 - 19196539
AN - SCOPUS:67449107209
SN - 1353-8020
VL - 15
SP - 430
EP - 434
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 6
ER -