A Pilot Mitochondrial Genome-Wide Association on Migraine Among Saudi Arabians

Lubna Al Asoom; Johra Khan; Ahmad Al Sunni; Nazish Rafique; Rabia Latif; Majed Alabdali; Sayed AbdulAzeez; J Francis Borgio

doi:10.2147/IJGM.S371707

A Pilot Mitochondrial Genome-Wide Association on Migraine Among Saudi Arabians

Int J Gen Med. 2022 Jul 21:15:6249-6258. doi: 10.2147/IJGM.S371707. eCollection 2022.

Authors

Lubna Al Asoom¹, Johra Khan^{2

3}, Ahmad Al Sunni¹, Nazish Rafique¹, Rabia Latif¹, Majed Alabdali⁴, Sayed AbdulAzeez⁵, J Francis Borgio⁵

Affiliations

¹ Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, 31541, Saudi Arabia.
² Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia.
³ Health and Basic Sciences Research Center, Majmaah University, Majmaah, 11952, Saudi Arabia.
⁴ Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, 31952, Saudi Arabia.
⁵ Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.

Abstract

Background: Mitochondrial DNA (mtDNA) mutations have been reported in multiple neurological diseases and helped to explain the pathophysiology of these diseases. Similarly, variations in mtDNA might exist in migraine and can explain the effect of low ATP production in the neurons on the initiation of migraine attack. Therefore, in the current study we aim to explore the association of mtDNA mutations on migraine in the Saudi population.

Subjects and methods: Over 1950 young Saudi female students were screened for migraine, among that a total of 103 satisfied the ICHD-3 criteria. However, 20 migraine cases confirmed in the neurology clinic and gave consent to participate in the study. Another 20 age-matched healthy controls were also recruited. Mitochondrial sequence variations were filtered from exome sequencing using NCBI GenBank Reference Sequence: NC_012920.1 and analysed using MITOMAP. Genes with significant single nucleotide polymorphisms (SNPs) were investigated by the gene functional classification tool DAVID and functional enrichment analysis of protein-protein interaction networks through STRING 11.5 for the most significant associated genes.

Results: Genome wide analysis of the mitochondrial sequence variations between the patients with migraine and control revealed the association of 30 SNPs (p < 0.05) in the mitochondrial genome. The highest significance (p = 0.001033) was observed in a coding SNP (rs1603225278) in the CYTB gene and rs386829281 in the region of origin of replication. Twenty-four significant SNPs were in the coding region of nine (ND5, ND4, COX2, COX1, ND3, CYTB, COX3, ND2 and ND1) genes.

Conclusion: This is the first study to demonstrate the association of mtDNA variations with migraine in the Saudi population. The current findings will help to highlight the significance of mtDNA mutations to migraine pathophysiology and will serve as a reference data for larger national and international studies.

Keywords: CYTB gene; Saudi Arabia; migraine; mitochondrial DNA; mtDNA variations.

Grants and funding

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number (IFP-2020-46).