Bashir Aadil, Saleem Shiekh, Wani Maqbool, Rasool Roohi, Wani Irfan Yousuf, Gulnar Azhara, Verma Sawan
Department of Neurology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
Department of Immunology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
Indian J Hum Genet. 2014 Jan;20(1):59-63. doi: 10.4103/0971-6866.132757.
Migraine is a chronic, neurovascular polygenic disease where genetic and environmental factors are involved in its etiology. Dysfunction of neuronal ion transportation can provide a model for predisposition for common forms of migraine. Mutations in genes encoding ion channels disturb the rhythmic function of exposed tissue that may also explain the episodic nature of migraine. Our aim was to study the single nucleotide polymorphisms of CACNA1A gene in migraine patients.
The subjects were the patients of migraine, in the age range of 18-80 years, diagnosed by a Neurologist, as per the diagnostic criteria of International Headache Society (IHS) Classification 2004 after excluding other causes of headache by clinical examination and relevant investigations. The controls were the age and sex matched healthy persons from the same population excluding the relatives of patients. Only those patients and the controls, who voluntarily participated in the study, were taken and their blood samples were taken for the study. Deoxyribonucleic acid (DNA) extraction was performed according to the manufacturer's protocol for Qiagen DNA extraction kits (Qiagen, Hilden, NRW, Germany). DNA content was quantified by spectrophotometric absorption (Nanodrop Spectrophotometer, BioLab, Scoresby, VIC, Australia). Polymerase chain reaction was performed using an iCycler Thermal Cycler (Bio.Rad, Hercules, CA, USA). The polymorphic analysis of CACNA1A gene was carried out by two methods: Restriction fragment length polymorphism and sequencing.
The study included a total of 25 patients of migraine, diagnosed on out-patient department basis as per IHS Classification 2004 and compared with age and sex matched 25 healthy controls. Most of the patients 23 (92%) were below the age of 50 years. 20 of the patients (80%) were females and 5 (20%) were males. The polymorphic analysis of CACNA1A gene revealed the presence of only the wild form of the gene for the codon E993V in both case and control groups.
In our study, we could not find any polymorphism of CACNA1A gene in the selected patients. Instead the wild type of genotype was found in both patients and controls. This negative result presented here, implies that if the CACNA1A gene is involved in typical migraine (with and without aura), its contribution is very modest and therefore difficult to discern. Nevertheless, there are other genes that could be considered potential candidates for typical migraine susceptibility for which further research is needed.
偏头痛是一种慢性神经血管多基因疾病，其病因涉及遗传和环境因素。神经元离子转运功能障碍可为常见偏头痛类型的易感性提供模型。编码离子通道的基因突变会扰乱暴露组织的节律功能，这也可能解释偏头痛的发作性本质。我们的目的是研究偏头痛患者中CACNA1A基因的单核苷酸多态性。
研究对象为年龄在18 - 80岁之间的偏头痛患者，由神经科医生根据国际头痛协会（IHS）2004年分类的诊断标准进行诊断，通过临床检查和相关调查排除其他头痛原因。对照组为来自同一人群、年龄和性别匹配的健康人，排除患者亲属。仅纳入自愿参与研究的患者和对照组，并采集他们的血液样本用于研究。按照Qiagen DNA提取试剂盒（Qiagen，德国希尔德，北莱茵 - 威斯特法伦州）制造商的方案进行脱氧核糖核酸（DNA）提取。通过分光光度吸收法（Nanodrop分光光度计，澳大利亚维多利亚州斯科斯比市BioLab）对DNA含量进行定量。使用iCycler热循环仪（美国加利福尼亚州赫拉克勒斯市Bio.Rad）进行聚合酶链反应。通过两种方法对CACNA1A基因进行多态性分析：限制性片段长度多态性和测序。
该研究共纳入25例偏头痛患者，根据IHS 2004年分类在门诊诊断，并与年龄和性别匹配的25名健康对照进行比较。大多数患者23例（92%）年龄在50岁以下。患者中20例（80%）为女性，5例（20%）为男性。CACNA1A基因的多态性分析显示，病例组和对照组中该基因密码子E993V仅存在野生型。
在我们的研究中，在所选择的患者中未发现CACNA1A基因的任何多态性。相反，在患者和对照组中均发现了野生型基因型。此处呈现的这一阴性结果表明，如果CACNA1A基因参与典型偏头痛（有或无先兆），其作用非常微小，因此难以辨别。然而，还有其他基因可被视为典型偏头痛易感性的潜在候选基因，对此需要进一步研究。
