TY - JOUR
T1 - Association of α-, β-, and γ-synuclein with diffuse lewy body disease
AU - Nishioka, Kenya
AU - Wider, Christian
AU - Vilariño-Güell, Carles
AU - Soto-Ortolaza, Alexandra I.
AU - Lincoln, Sarah J.
AU - Kachergus, Jennifer M.
AU - Jasinska-Myga, Barbara
AU - Ross, Owen A.
AU - Rajput, Alex
AU - Robinson, Christopher A.
AU - Ferman, Tanis J.
AU - Wszolek, Zbigniew K.
AU - Dickson, Dennis W.
AU - Farrer, Matthew J.
PY - 2010/8
Y1 - 2010/8
N2 - Objective: To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design: Case-control study. Subjects: A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions: Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associationswere determined using χ2 or Fisher exact tests. Results: Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequenceconserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion: These findings suggest that variants in all 3members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series.
AB - Objective: To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design: Case-control study. Subjects: A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions: Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associationswere determined using χ2 or Fisher exact tests. Results: Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequenceconserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion: These findings suggest that variants in all 3members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series.
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U2 - 10.1001/archneurol.2010.177
DO - 10.1001/archneurol.2010.177
M3 - Article
C2 - 20697047
AN - SCOPUS:77955447233
SN - 0003-9942
VL - 67
SP - 970
EP - 975
JO - Archives of neurology
JF - Archives of neurology
IS - 8
ER -