title: A search for SNCA 3' UTR variants identified SNP rs356165 as a determinant of disease risk and onset age in Parkinson's disease.
abstract: Alpha-synuclein gene (SNCA) polymorphisms have been associated with the common sporadic form of Parkinson's disease (PD). We searched for DNA variants at the SNCA 3' UTR through single strand conformation analysis and direct sequencing in a cohort of Spanish PD patients and controls. We have genotyped the rs356165 SNCA 3' UTR polymorphism in a total of 1,135 PD patients and 772 healthy controls from two Spanish cohorts (Asturias and Navarre). We identified six SNCA 3' UTR variants. Single nucleotide polymorphism (SNP) rs356165 was significantly associated with PD risk in the Spanish cohort (p = 0.0001; odd ratio = 1.37, 95%CI = 1.19-1.58). This SNP was also significantly associated with early age at onset of PD. Our work highlights rs356165 as an important determinant of the risk of developing PD and early age at onset and encourages future research to identify a functional effect on SNCA expression.
authors.affiliation: Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, 33006, Oviedo, Spain.
authors.forename: Lucía F
authors.initials: LF
authors.lastname: Cardo
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Lorena
authors.initials: L
authors.lastname: de Mena
authors.forename: René
authors.initials: R
authors.lastname: Ribacoba
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Germán
authors.initials: G
authors.lastname: Moris
authors.forename: Manuel
authors.initials: M
authors.lastname: Menéndez
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C497604:SNCA protein, human; D051844:alpha-Synuclein
references.citation: Science. 1997 Jun 27;276(5321):2045-7
references.pmid: 9197268
references.citation: Lancet Neurol. 2006 Jun;5(6):525-35
references.pmid: 16713924
references.citation: Ann Neurol. 2004 Oct;56(4):591-5
references.pmid: 15455394
references.citation: Ann Neurol. 2005 Apr;57(4):535-41
references.pmid: 15786467
references.citation: Ann Neurol. 2003;53 Suppl 3:S16-23; discussion S23-5
references.pmid: 12666095
references.citation: Ann Hum Genet. 2010 Mar;74(2):97-109
references.pmid: 20070850
references.citation: Acta Neurol Scand. 2008 Nov;118(5):320-7
references.pmid: 18485051
references.citation: Brain Res. 2010 Jul 30;1346:262-5
references.pmid: 20513365
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13052-7
references.pmid: 19628698
references.citation: Hum Mol Genet. 2006 Apr 1;15(7):1151-8
references.pmid: 16500997
references.citation: Hum Mol Genet. 2009 Dec 15;18(24):4801-7
references.pmid: 19776031
references.citation: Eur J Neurol. 2006 Apr;13(4):391-4
references.pmid: 16643318
references.citation: Nat Genet. 1998 Feb;18(2):106-8
references.pmid: 9462735
references.citation: Science. 2007 Aug 31;317(5842):1179-80
references.pmid: 17761871
references.citation: Nature. 1997 Aug 28;388(6645):839-40
references.pmid: 9278044
references.citation: Nat Genet. 2009 Dec;41(12):1308-12
references.pmid: 19915575
references.citation: Ann Neurol. 2004 Feb;55(2):164-73
references.pmid: 14755719
references.citation: Nat Genet. 2009 Dec;41(12):1303-7
references.pmid: 19915576
references.citation: Lancet Neurol. 2009 Dec;8(12):1150-7
references.pmid: 19909913
references.citation: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references.pmid: 1564476
references.citation: Neurosci Lett. 2009 Sep 18;461(2):196-201
references.pmid: 19540308
references.citation: Neurogenetics. 2011 Feb;12(1):59-64
references.pmid: 21046180
references.citation: Mov Disord. 2011 Apr;26(5):819-23
references.pmid: 21425343
references.citation: Mov Disord. 2001 Nov;16(6):1115-9
references.pmid: 11748744
references.citation: Am J Hum Genet. 2008 Feb;82(2):283-9
references.pmid: 18252210
references.citation: J Biol Chem. 2010 Apr 23;285(17):12726-34
references.pmid: 20106983