Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism and Migraine Susceptibility and Phenotypes:...

Background/Objectives: Migraine is a complex neurovascular disorder with a multifactorial genetic basis and remains a leading cause of neurological disability worldwide. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been implicated in vascular regulation and neurovascular reactivity; however, its role in migraine susceptibility and clinical expression remains unclear. This study aimed to evaluate the association between ACE I/D polymorphism and migraine susceptibility and clinical phenotypes in a diverse clinical cohort. Methods: A case-control study was conducted including 183 participants, comprising clinically diagnosed migraine patients (n = 82) and age- and sex-matched controls (n = 101). Genomic DNA was extracted from peripheral blood samples, and ACE I/D genotyping was performed using polymerase chain reaction. Genotype distribution was compared using chi-square tests, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Overall genotype frequencies were Deletion/Deletion (DD) 43.7%, ID 38.8%, and Insertion/Insertion (II) 17.5%. Genotype distributions were comparable between migraine patients and controls (χ² ≈ 0.92, p = 0.632). No statistically significant associations were identified between ACE I/D polymorphism and migraine susceptibility, genotype models, or migraine subtypes. However, the II genotype was associated with higher Migraine Disability Assessment (MIDAS) scores among migraine patients. Conclusions: The ACE I/D polymorphism was not associated with migraine susceptibility or clinical phenotypes in this cohort. These findings suggest that ACE I/D polymorphism does not appear to be a major determinant of migraine susceptibility in this cohort. The results highlight the need to investigate broader genetic and molecular mechanisms and support the application of integrative genomic approaches to better understand migraine heterogeneity and inform precision medicine strategies.