CACNA1A Genetic Variants and Their Potential Involvement in Migraine Pathogenesis

Migraine is a prevalent neurological disorder that affects over 1 billion individuals worldwide. The pathogenesis of migraine remains incompletely understood, though evidence suggests a multifactorial etiology involving genetic factors. The CACNA1A gene has been implicated in rare forms of Familial Hemiplegic Migraine (FHM). This study aimed to investigate the role of CACNA1A variants in individuals with and without a family history of migraine. We genotyped 150 subjects (100 migraine patients: 50 with migraine without aura (MO), 50 with migraine with aura (MA) and 50 controls) for six CACNA1A variants using Sanger sequencing. Statistical analyses were performed in Statistica (p < 0.05). The CADD v1.7 model was used to assess the potential pathogenicity of novel variants. Three variants described in databases (rs10405121, rs894252513, and rs1012663275) and three novel variants (ch19:13228374 G > C, ch19:13228428 G > C, and ch19:13228348 A > T) were identified. The rs10405121 variant was associated with both migraine types, with the homozygous AA genotype exclusively found in familial cases. Abnormal genotype of rs894252513 and rs1012663275 were detected only in familial cases with MO. The novel variants were observed exclusively in patients with a family history of migraine, suggesting their potential relevance to inherited migraine pathogenesis. Novel variants may contribute to migraine pathogenesis by altering calcium channel function and lowering the threshold for cortical spreading depression (CSD).