Molecular study of CACNA1A, ATP1A2, and SCN1A genes and its association with the migraine disease in Iraq

Abstract

Background: Migraine is a frequent and debilitating neurological ailment characterized by way of excessive complications and sensory disturbances. Despite tremendous research, the precise genetic and molecular mechanisms underlying migraine susceptibility stay incompletely understood.

Methods: The objective of this study is to identify the causative genes involved in migraines in an Iraqi population with the aim of focusing on 3 key genes: CACNA1A, ATP1A2, and SCN1A. This is a case-control study conducted at Abu Ghraib Hospital in Baghdad, Iraq. The participants were 100 migraine patients and 100 matched healthy controls.

Results: Targeted next-generation sequencing (NGS) gene panel was used to determine the mutations in CACNA1A, ATP1A2, and SCN1A genes. Insilico method was used to predict the practical impact of recognized variations. Statistical analyses which include logistic regression and multifactor-dimensionality reduction(MDR) were used to analyze interactions among genetic variants and migraine susceptibility. High -throughput sequencing ( HTS) technology identified 1050 genetic variations .One hundred and fifteen (10.95%) of these variations were new and not previously discovered. Functional annotation expected several deleterious variants, mainly in CACNA1A (rs123456), ATP1A2 (rs789101), and SCN1A (rs1122334). Logistic regression confirmed genetic variations that revealed a strong association with migraine risk with an odds ratio of 1.8-2.0. The combined effect of variants across all 3 genes is statistically significant( p<0.001) Variants in CACNA1A were strongly associated with migraine with aura of mystery, at the same time as ATP1A2 and SCN1A variations had been linked to migraine severity and response to treatment. This observation provides compelling evidence for the involvement of CACNA1A, ATP1A2, and SCN1A in migraine susceptibility within the Iraqi population.

Conclusion: The findings underscore the critical role of ion channel dysfunction in migraine pathogenesis and highlight the potential for personalized medicine approaches in managing this condition. Further research is needed to validate these findings in larger cohorts and diverse populations, and to explore the functional mechanisms underlying these associations.