Association of GABRA1 Polymorphisms with Migraine with Aura: A Preliminary Case–Control Study in a Turkish Cohort

ABSTRACT Aim: The objective of this study is to ascertain the association between two prevalent GABRA1 polymorphisms (rs12658835, rs35166395) and migraine with aura . In addition, the investigation will encompass the clinical characteristics of the condition, including trigger patterns and family history. Material and Method: 108 persons with clinically proven migraine with aura and 107 demographically matched healthy controls were enrolled in a multicenter case-control study (Atatürk University Faculty of Medicine Neurology Department and Palandöken State Hospital Neurology Outpatient Clinic; 01 Feb–01 Jun 2013). Sociodemographics, migraine characteristics, triggers, and family history were recorded through structured in-person interviews. A sample of peripheral blood was used to extract genomic DNA. SNP genotyping was performed using a validated real-time PCR allelic discrimination kit for GABRA1 rs12658835 and rs35166395. The case/control status was hidden from the lab staff. Results: The migraine with aura cohort was predominantly female (82.4%) with a mean age of 33.8 ± 12.4 years; the control group exhibited a similar distribution of sex and age (both p > 0.05, Mann–Whitney U for age). rs12658835 exhibited an excess of mutant genotype in migraine with aura (7.4%, 8/108) in comparison to the control group (0%, 0/107), p = 0.007. The genotype distributions of rs35166395 (wild/mutant/heterozygous: 60/16/24% in migraine with aura vs. 65/13/22% in controls) did not differ (p > 0.05). In the context of migraine with aura cases, a family history of migraine was associated with an elevated probability of activity-impairing attacks (69.4% overall; OR ≈ 2.06; p = 0.02) and pain exacerbation during physical activity (p = 0.02). No substantial gender-based disparities were observed in other clinical characteristics. Conclusion: In this Turkish cohort, the GABRA1 rs12658835 variant is associated with migraine with aura, whereas the rs35166395 variant is not. Familial predisposition is linked to more debilitating attacks and exertional exacerbation, highlighting the genetic factors that contribute to the severity of the phenotype and the potential GABAergic mechanisms involved in the pathophysiology of migraine with aura.