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

Abstract

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.

Keywords

• Migraine
• Polimorphism
• GABRA1

GABRA1 Polimorfizmlerinin Auralı Migren ile İlişkisi: Türk Kohortunda Ön Nitelikli Olgu-Kontrol Çalışması

Abstract

Amaç: Bu çalışmanın amacı, GABRA1 genindeki iki yaygın polimorfizmin (rs12658835, rs35166395) auralı migren ile ilişkisini saptamaktır. Ayrıca tetikleyici paternler ve aile öyküsü dâhil olmak üzere klinik özellikler incelenmiştir. Gereç ve Yöntem: Çok merkezli olgu–kontrol tasarımında (Atatürk Üniversitesi Tıp Fakültesi Nöroloji Anabilim Dalı ve Palandöken Devlet Hastanesi Nöroloji Polikliniği; 01.02.2013–01.06.2013) klinik olarak doğrulanmış auralı migren tanılı 108 birey ve demografik olarak eşleştirilmiş 107 sağlıklı kontrol çalışmaya alındı. Yapılandırılmış yüz yüze görüşmelerle sosyodemografik veriler, migren özellikleri, tetikleyiciler ve aile öyküsü kaydedildi. Periferik kandan genomik DNA izole edildi. GABRA1 rs12658835 ve rs35166395 için gerçek zamanlı PCR alel-ayrım kiti kullanılarak SNP genotiplemesi yapıldı. Laboratuvar personeli olgu/kontrol durumuna körlendi. Bulgular: Auralı migren grubu çoğunlukla kadındı (%82,4) ve ortalama yaş 33,8 ± 12,4 yıldı; kontrol grubunda yaş ve cinsiyet dağılımı benzerdi (her ikisi için p > 0,05, yaş için Mann–Whitney U). rs12658835 için auralı migren grubunda mutant genotip fazlalığı saptandı (%7,4; 8/108) ve bu fark kontrol grubuna kıyasla anlamlıydı (%0; 0/107; p = 0,007). rs35166395 genotip dağılımları (auralı migrende sırasıyla %60/%16/%24; kontrollerde %65/%13/%22) arasında anlamlı fark yoktu (p > 0,05). Auralı migren olgularında ailede migren öyküsü, aktiviteyi kısıtlayan ataklarla (toplam %69,4; OR ≈ 2,06; p = 0,02) ve fiziksel aktivite ile ağrı artışıyla (p = 0,02) ilişkili bulundu; diğer klinik özelliklerde cinsiyete göre belirgin fark saptanmadı. Sonuç: Bu Türk kohortunda GABRA1 rs12658835 varyantı auralı migren ile ilişkili bulunurken, rs35166395 ile ilişki izlenmedi. Ailevi yatkınlığın daha yıkıcı ataklar ve eforla alevlenme ile ilişkisi, fenotip şiddetine katkıda bulunan genetik etmenleri ve auralı migrenin patofizyolojisinde olası GABAerjik mekanizmaları desteklemektedir.

Keywords

• Migren
• Polimorfizm
• GABRA1

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