Methylation of alpha-synuclein in a Sudanese cohort

Yousuf Bakhit; Ina Schmitt; Ahlam Hamed; Etedal Ahmed A Ibrahim; Inaam N Mohamed; Sarah M El-Sadig; Maha A Elseed; Mohamed A Alebeed; Mutaz T Shaheen; Mohamed O Ibrahim; Ali A Elhassan; Khalid Eltom; Hiba A Ali; Yousuf A Ibrahim; Murad E Almak; Rayan Abubaker; Mohamed Anwer Ahmed; Ahmed A Abugrain; Salma M Elrasheed; Mawia A Omar; Mohamed A Almahal; Abubaker A MohamedSharif; Mohamed Y Tahir; Sawazen M Malik; Hazim S Eldirdiri; Reem J Khidir; Malaz T Mohamed; Abdelmohaymin Abdalla; Farouk Yassen Omer; Liena E O Elsayed; Haydar El Hadi Babikir; Elfateh Abd-Allah Bukhari; Osheik Seidi; Ullrich Wüllner

doi:10.1016/j.parkreldis.2022.05.009

Methylation of alpha-synuclein in a Sudanese cohort

Parkinsonism Relat Disord. 2022 Aug:101:6-8. doi: 10.1016/j.parkreldis.2022.05.009. Epub 2022 Jun 4.

Authors

Yousuf Bakhit¹, Ina Schmitt², Ahlam Hamed³, Etedal Ahmed A Ibrahim⁴, Inaam N Mohamed³, Sarah M El-Sadig⁵, Maha A Elseed³, Mohamed A Alebeed⁶, Mutaz T Shaheen⁶, Mohamed O Ibrahim⁷, Ali A Elhassan⁶, Khalid Eltom⁶, Hiba A Ali⁶, Yousuf A Ibrahim⁶, Murad E Almak⁸, Rayan Abubaker⁹, Mohamed Anwer Ahmed⁶, Ahmed A Abugrain⁶, Salma M Elrasheed⁶, Mawia A Omar⁶, Mohamed A Almahal⁶, Abubaker A MohamedSharif¹⁰, Mohamed Y Tahir⁶, Sawazen M Malik⁶, Hazim S Eldirdiri¹¹, Reem J Khidir⁶, Malaz T Mohamed⁶, Abdelmohaymin Abdalla⁶, Farouk Yassen Omer¹², Liena E O Elsayed¹³, Haydar El Hadi Babikir¹⁴, Elfateh Abd-Allah Bukhari¹⁵, Osheik Seidi⁵, Ullrich Wüllner¹⁶

Affiliations

¹ Department of Neurology, University Hospital Bonn, Germany; Department of Basic Medical Sciences, Faculty of Dentistry, University of Khartoum, Sudan; Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan. Electronic address: npgy1@yahoo.com.
² Department of Neurology, University Hospital Bonn, Germany.
³ Department of Paediatrics, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
⁴ Faculty of Medicine, Al Neelain University, Khartoum, Sudan, and The National Centre for Neurological Sciences, Sudan.
⁵ Department of Neurology, Soba Teaching Hospital, And Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
⁶ Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan.
⁷ Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan; Department of Biochemistry, Faculty of Medicine, Sudan University of Science and Technology, Khartoum, Sudan.
⁸ Department of Physiology, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
⁹ Department of Molecular Medicine, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan; Department of Molecular Biology, National University Biomedical Research Institute (NUBRI), National University, Khartoum, Sudan.
¹⁰ Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan; Department of Anatomy, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
¹¹ Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan; University of Bordeaux, INSERM, U1215, Neurocentre Magendie, Bordeaux, France.
¹² Department of Medicine, Neurology, Omdurman Islamic University, Khartoum, Sudan.
¹³ Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
¹⁴ Department of Paediatrics and Child Health, Faculty of Medicine, University of Gezira, Sudan.
¹⁵ Department of Neurology, Bashaier University Hospital, And Khartoum Teaching Hospital. Department of Medicine, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan.
¹⁶ Department of Neurology, University Hospital Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Electronic address: ullrich.wuellner@dzne.de.

PMID: 35728367
DOI: 10.1016/j.parkreldis.2022.05.009

Abstract

Background: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan.

Materials and methods: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCA_intron1 was performed as described earlier.

Results: Of the fourteen analyzed CpGs of SNCA_intron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P-values improved, when sporadic cases were excluded from the analysis.

Conclusion: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCA_intron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering.

Keywords: Methylation; Parkinson's disease; SNCA; Sudan.

MeSH terms

Adolescent
Adult
DNA
DNA Methylation / genetics
Epigenesis, Genetic
Humans
Middle Aged
Parkinson Disease* / genetics
Young Adult
alpha-Synuclein / genetics
alpha-Synuclein / metabolism*

Substances

SNCA protein, human
alpha-Synuclein
DNA