Age at onset in LRRK2-associated PD is modified by SNCA variants.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) and α-synuclein (SNCA) genes are known genetic causes of Parkinson's disease (PD). Recently, a genetic variant in SNCA has been associated with a lower age at onset in idiopathic PD (IPD). We genotyped the SNCA polymorphism rs356219 in 84 LRRK2-associated PD patients carrying the G2019S mutation. We found that a SNCA genetic variant is associated with an earlier age at onset in LRRK2-associated PD. Our results support the notion that SNCA variants can modify the pathogenic effect of LRRK2 mutations as described previously for IPD.
Parkinson's Disease and Movement Disorders Unit, Neurology Service-Hospital Clínic, Institut de Neurociències and Department of Medicine, Universitat de Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Teresa
T
Botta-Orfila
Mario
M
Ezquerra
Pau
P
Pastor
Rubén
R
Fernández-Santiago
Claustre
C
Pont-Sunyer
Yaroslau
Y
Compta
Oswaldo
O
Lorenzo-Betancor
Lluis
L
Samaranch
Maria José
MJ
Martí
Francesc
F
Valldeoriola
Matilde
M
Calopa
Manel
M
Fernández
Miquel
M
Aguilar
Oriol
O
de Fabregas
Jorge
J
Hernández-Vara
Eduard
E
Tolosa
D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
C497604:SNCA protein, human; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases