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A Search for SNCA 3′ UTR Variants Identified SNP rs356165 as a Determinant of Disease Risk and Onset Age in Parkinson’s Disease

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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.

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Acknowledgments

Authors thank the “Fundacion Parkinson Asturias” and “Obra Social Cajastur” for their support. This work was supported by grants from the Spanish “Fondo de Investigaciones Sanitarias-Fondos FEDER” European Union (FIS-05/008 and 08/0915). LFC and LDM are predoctoral fellowships of FICYT-Principado de Asturias. LS held a “Torres Quevedo” fellowship from the Spanish Ministry of Science and Technology, co-financed by the European Social Fund. This study was supported by a grant from the Spanish Ministry of Education and Science (SAF2006-10126, 2006–2009) by the project 061131 from the “Fundació La Marató de TV3” and by the UTE project FIMA, Spain to PP.

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The authors report no conflicts of interest.

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Authors and Affiliations

  1. Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, 33006, Oviedo, Spain

    Lucía F. Cardo, Eliecer Coto, Lorena de Mena, Marta Díaz, Ana I. Corao & Victoria Alvarez

  2. Neurología, Hospitales Universitario Central Asturias, and Álvarez Buylla-Mieres, Asturias, Spain

    René Ribacoba, Germán Moris & Manuel Menéndez

  3. Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Clínica Universitaria de Navarra, Pamplona, Spain

    Oswaldo Lorenzo-Betancor, Pau Pastor & LLuis Samaranch

  4. Department of Medicine, University of Oviedo, Oviedo, Spain

    Eliecer Coto

  5. Department of Neurology, Clínica Universitaria de Navarra, Pamplona, Spain

    Oswaldo Lorenzo-Betancor & Pau Pastor

  6. Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA

    Ignacio F. Mata

  7. Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA

    Ignacio F. Mata

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  1. Lucía F. Cardo
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  2. Eliecer Coto
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  3. Lorena de Mena
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  8. Ignacio F. Mata
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  10. Germán Moris
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  11. Manuel Menéndez
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Corresponding author

Correspondence to Victoria Alvarez.

Electronic Supplementary Material

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Supplementary Table 1

Primers designed to amplify the four 3´UTR SNCA fragments. SNP rs356165 was genotyped through amplification with fragment 4 primers, followed by digestion with TaiI and electrophoresis on 4% agarose gel to visualize the two alleles: A 273 bp and G 199 + 74 bp (DOC 32 kb)

Supplementary Fig. 1

a PCR-RFLP genotypes for the rs356165 SNP. b SSCA patterns of heterozygotes (arrows) for the c.404 C>T and the c.*139 T>G (SNP rs10024743). c DNA sequences showing the c.404 C>T and the c.*575_579 deletion (DOC 79 kb)

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Cardo, L.F., Coto, E., de Mena, L. et al. A Search for SNCA 3′ UTR Variants Identified SNP rs356165 as a Determinant of Disease Risk and Onset Age in Parkinson’s Disease. J Mol Neurosci 47, 425–430 (2012). https://doi.org/10.1007/s12031-011-9669-1

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