Study of the Rep-1 microsatellite of the alpha-synuclein gene in patients with idiopathic Parkinson's disease

Authors

Keywords:

Parkinson's disease, alpha-synuclein gene, Rep-1 microsatellite

Abstract

Introduction: The search for a reliable biomarker for the diagnosis of Parkinson's disease (PD) is crucial for understanding the illness and preventing disability. In the alpha synuclein (α-Syn) gene, a microsatellite-type dinucleotide called Rep-1 has been identified that could be used as a risk biomarker in PD.  Objective: The aimed of this study was to identify the variants of the Rep-1 microsatellite of the α-Syn gene in patients with PD. Material and Methods: Thirty patients (15 with PD and 15 controls) were recruited from the neurology clinic and the outpatient clinic, respectively. Blood sampling was taken to extract genomic DNA. The genotyping of the repeated dinucleotides was performed with the GENESCAN analysis software on an ABI PRISM 3500xL DNA sequencer. A t-student was used to compare the data, and the qualitative variables were analyzed through a χ2 and to obtain probability risk.  Results: From the 15 patients diagnosed with PD, 10 (66.7%) were women and 5 (33.3%) were men, with an average age of 65 ± 6.36 years. The most frequent α-Syn gene variants were the 265 bp variant with 63.3% and the 267 bp variant with 20% in both groups. There was a greater significance of the longer alleles in PD patients with a risk probability of 1.37 (p=0.09). Conclusion: The identification of the Rep-1 microsatellite of the α-Syn gene showed a trend of larger alleles (>265 bp) as a risk factor for idiopathic PD.

Author Biographies

Cristian G Marroquí-Sánchez, undergraduate student of Instituto Nacional de Rehabilitación

neurocience coordination

Rogelio Paniagua-Pérez, Institituto Nacional de Rehabilitación

biochemistry service

Paul Carrillo-Mora, instituto nacional de rehabilitación

neuroscience coordination

José A Martínez-Cortez , instituto nacional de rehabilitación

neurology service

Claudia Hernández-Arenas , instituto nacional de rehabilitación

acquired brain injury service

Antonio Verduzco-Mendoza, instituto nacional de rehabilitación

B. and experimental surgery

Adriana Olmos-Hernández , Instituto Nacional de Rehabilitación

B and experimental surgery

Alberto Ávila-Luna, Instituto Nacional de Rehabilitación

basic neuroscience coordination

Antonio Bueno-Nava, Instituto Nacional de Rehabilitación

basic neuroscience coordination

References

Bibliografía

- Morris HS, Spillantini MG, Sue CM, and Williams-Gray CH. The pathogenesis of Parkinson´s disease. Lancet 2024; 403(10423): 293-304.

- Lee A., Gilbert RM. Epidemiology of Parkinson disease. Neurol Clin 2016; 34: 955-965.

- Schapira AHV., Chaudhuri KR., and Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci 2017; 18(7): 435-450.

- Sauerbier A., Jenner P., Todorova A., Chaudhuri KR., Non motor subtypes and Parkinson´s disease. Parkinsonism Relat Disord 2016; 22 Suppl 1:S41-S46.

- Kalia LV., Lang AE. Parkinson´s disease. Lancet 2015; 386: 896-912.

- Lees AJ., Hardy J and Revez T. Parkinson´s disease. Lancet 2009; 373:2055-2066.

- Shahmoradian SH., Lewis AJ., Genoud C., Hench J., Moors TE., Navarro PP., et al. Lewy pathology in Parkinson´s disease consists of crowded organelles and lipid membranas. Nat Neurosci 2019; 22(7): 1099-1109.

- Tolosa E., Garrido A., Scholz SW., and Poewe W. Challenges in the diagnosis of Parkinson´s disease. Lancet Neurol 2021; 20(5): 385-397.

- Jankovik J., and Tan EK. Parkinson´s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry 2020; 91(8): 795-808.

- Correia Guedes L., Mestre T., Outeiro TF., and Ferreira JJ. Are genetic and Idiopathic formo f Parkinson´s disease the same disease?. J Neurochem 2020; 152(5):515-522.

- Stefanis L. α-Synuclein in Parkinson´s disease. Cold Spring Harb perspect Med 2012; 2(2):a 009399.

- Tofaris GK. Initiation and progression of Alpha-synuclein pathology in Parkinson´s disease. Cell Mol Life Sci 2022; 79(4):210.

- Henderson MX., Trojanowski JQ., Lee VM. Alpha-synuclein pathology in Parkinson´s disease and related Alpha synucleinopathies. Neurosci lett 2019; 709: 134316.

- Kim S., Jeon BS., Heo C., Im PS., Ahn TB., Seo JH., et al. Alpha-synuclein induces apoptosis by altered expresion in human peripheral lymphocyte in Parkinson´s disease. FASEB J 2004; 18(13): 1615-1617.

- Winkler S., Hagenah J., Lincoln S., Heckman M., Haugarvoll K., Lohmann-Hedrich K., et al. Alpha-Synuclein and Parkinson disease susceptibility. Neurology 2007; 69(18):1745-1750.

- Pals P., Lincoln S., Manning J., Heckman M., Skipper L., Hulihan M., et al. Alpha synuclein promoter confers susceptibility to Parkison´s disease. ANN Neurol 2004; 56(4):591-595.

- Hoehn MM., Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967; 17(5): 427-442.

- Yong AC., Tan YJ., Zhao Y., Lu Z., Ng EY., Ng SY., et al. SNCA Rep 1 microsatellite length influences no-motor symptoms in early Parkinson´s disease. Aging 2020; 12(20):20880-20887.

- Beitz JM. Parkinson´s disease: a review. Front Biosci 2014; 6: 65-74.

- Sherer TB., Betarbet R., Greenamyre JT. Pathogenesis of Parkinson´s disease. Curr Opin Invest Drugs 2001; 2: 657-662.

- Xia Y., Rohan de Silva HA., Rosi BL., Yamamoto LH., Rimmler JB., Pericak-Vance MA., et al. Genetic studies in Alzheimer´s disease with an NACP/Alpha-synuclein polymorphism. Ann Neurol 1996; 40:207-215.

- Brighina L., Schneider NK., Lesnick TG., de Andrade M., Cunningham JM., Mrazek D., et al. Alpha-synuclein, alcohol use disorders, and Parkinson disease: a case-control study. Parkinsonism Relat Disord 2009; 15: 430-434.

- Spadafora P., Annesi G., Pasqua AA., Serra P., Ciro Candiano IC., Carrideo S., et al. NACP-REP1 polymorphism is not involved in Parkinson´s disease: a case-control study in a population sample from southern italy. Neurosci Lett 2003; 351: 75-78.

- Gatto NM., Rhodes SL., Manthripragada AD., Bronstein J., Cockburn M., Farrer M., et al. Alpha-synuclein gene may interact with environmental factors in increasingrisk of Partkinson´s disease. Neuroepidemiology 2010; 35:191-195.

- Iakovenko EV., Abramycheva N., Fedotova E., and Illarioshkin SN. The SNCA-Rep1 polimorphic Locus: Association with the Risk of Parkinson´s Desease and SNCA Gene Methylation. Acta Naturae 2020; 12(2): 105-110.

- Linnertz C., Saucer L., Ge D., Cronin KD, Burke JR., Browndyke JN., Et al. Genetic regulation of Alpha-synuclein mRNA expresión in various human brain tissues. PLoS One 2009; 4(10): e7480.

- Fuchs J., Tichopad A., Golub Y., Munz M., Schweitzer KJ., Wolf B. et al. Faseb J 2008;22(5): 1327-1334.

- Cronin KD., Ge D., Manninger P., Linnertz C., Rossoshek A., Orrison BM., et al. Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human Alpha-synuclein in trasgenic mouse brain. Hum Mol Genet 2009; 18(17): 3274-3285.

- Zhang N., Yan Z., Xin H., Shao S., Xue S., Cespuglio R. et al. Relationship among α-synuclein, aging and inflammation in Parkinson´s disease. Exp Ther Med 2023; 27(1): 1-16.

- Coleman C and Martin I. Unraveling Parkinson´s disease neurodegeneration: Does aging hold the clue?. Parkinsons Dis 2022; 12(8): 2321-2338.

- Hou Y., Dan X., Babbar M., Wei Y., Hasselbalch SG., Croteau DL., et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019; 15(10):565-581.

- Patel R and Kompoliti K. Sex and gender differences in Parkinson´s disease. Neurol Clin 2023; 41(2): 371-379.

- Cerri S., Mus L and Blandini F. Parkinson´s disease in women and Men: What´s the difference?. J Parkinsons Dis 2019; 9(3): 501-515.

- Huang X., Chen H., Miller WC., Mailman RB., Woodard JL., Chen PC., et al. Lower low-density lipoprotein colesterol levels are associated with Parkinson´s disease. Mov Disord 2007; 22:377-381.

- Huang X., Abbott RD., Petrovitch H., Mailman RB., and Ross GW. Low LDL colesterol and increased risk of Parkinson´s disease: prospective results from Honolulu-Asia aging study. Mov Disord 2008; 23:1013-1018.

- Nam GE., Kim SM., Ha K., Kim NH., Chung HS., Kim JW., et al. Metabolic síndrome and risk of Parkinson disease: a nationwide cohort study. PLos Med 2018; 15:e1002640.

- de Lau LM., Koudstaal PJ., Hofman A., and Breteler MM. Serum colesterol level and the risk of Parkinson´s disease. Am J Epidemiol 2006; 164:998-1002.

- Huang X., Alonso A., Gou X., Umbach DM., Lichtenstein ML., Ballantyne CM., et al. Statins, plasma colesterol, and risk of Parkinson´s disease: a prospective study. Mov Disord 2015; 30:552-559.

Published

2024-11-29

How to Cite

1.
Marroquí-Sánchez CG, Paniagua-Pérez R, Carrillo-Mora P, Martínez-Cortez JA, Hernández-Arenas C, Verduzco-Mendoza A, et al. Study of the Rep-1 microsatellite of the alpha-synuclein gene in patients with idiopathic Parkinson’s disease. InDiscap [Internet]. 2024 Nov. 29 [cited 2024 Dec. 4];. Available from: http://dsm.inr.gob.mx/indiscap/index.php/INDISCAP/article/view/58

Issue

Section

Original articles

Most read articles by the same author(s)

Similar Articles

<< < 1 2 3 4 > >> 

You may also start an advanced similarity search for this article.