Kowalska Marta, Kapelusiak-Pielok Magdalena, Grzelak Teresa, Wypasek Ewa, Kozubski Wojciech, Dorszewska Jolanta
Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Chair and Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Front Mol Neurosci. 2018 Jun 5;11:191. doi: 10.3389/fnmol.2018.00191. eCollection 2018.
Migraine is one of the most common primary headache disorders that affects 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura (MA) and migraine without aura (MO). Both serotonergic and hypocretinergic systems are involved in the migraine pathomechanism. Polymorphisms in the serotonin transporter gene () and the hypocretin receptor 1 gene () may be risk factors for migraine development due to their ability to affect serotonin and hypocretin-1 (HCRT-1) concentrations. The aim of the study was to analyze, for the first time in the Polish population, the 5-HT transporter linked polymorphic region (5-HTTLPR) in , G1222A (rs2271933) and the never before studied *G29A (rs41263963) polymorphisms in the gene, as well as the 5-HT and hypocretin-1 plasma concentrations in migraine patients (MA, MO) and control subjects. The study included 123 patients that were diagnosed with migraine and 123 control subjects. Methods such as PCR, HRMA and sequencing were used for genotyping, while 5-HT was determined by HPLC/EC and hypocretin-1 by ELISA. No significant differences were observed in 5-HTTLPR frequencies. The A allele of G1222A occurred more often in MO, while the GA genotype of *G29A was more frequent among MA when compared to control group ( < 0.05). The mean age of migraine onset in individuals with *G29A was 18 years old for patients with MA and 26 years old for MO patients. The localization and type of polymorphisms (G1222A-missense variant in exon 7, *G29A-3'UTR variant) may predispose patients to the clinical subtype of migraine: MO or MA, respectively. In control subjects, the short allele of 5-HTTLPR tended to decrease the 5-HT concentration, while the A allele of G1222A decreased both 5-HT and hypocretin-1 levels. Serotonin concentrations differed in terms of clinical features of migraine. The relation between genotypes of 5-HTTLPR, G1222A, and 5-HT concentrations may bedisturbed in migraine. It seems that *G29A is more strongly associated with regulating the 5-HT in patients with MA than MO, and therefore may contribute to the early age of onset for migraine.
偏头痛是最常见的原发性头痛疾病之一，影响着11%的成年人口。该疾病主要分为两种临床亚型：伴先兆偏头痛（MA）和无先兆偏头痛（MO）。血清素能系统和下丘脑泌素能系统均参与偏头痛的发病机制。血清素转运体基因（）和下丘脑泌素受体1基因（）的多态性可能是偏头痛发病的危险因素，因为它们能够影响血清素和下丘脑泌素-1（HCRT-1）的浓度。本研究的目的是首次在波兰人群中分析血清素转运体相关多态性区域（5-HTTLPR）在基因中的情况、G1222A（rs2271933）以及此前从未研究过的基因中的G29A（rs41263963）多态性，以及偏头痛患者（MA、MO）和对照受试者的血浆血清素和下丘脑泌素-1浓度。该研究纳入了123例被诊断为偏头痛的患者和123名对照受试者。采用PCR、HRMA和测序等方法进行基因分型，血清素通过HPLC/EC测定，下丘脑泌素-1通过ELISA测定。在5-HTTLPR频率方面未观察到显著差异。与对照组相比，G1222A的A等位基因在MO中出现得更频繁，而G29A的GA基因型在MA中更常见（<0.05）。对于*G29A，MA患者偏头痛发作的平均年龄为18岁，MO患者为26岁。基因多态性（G1222A-外显子7中的错义变异，G29A-3'UTR变异）的定位和类型可能分别使患者易患偏头痛的临床亚型：MO或MA。在对照受试者中，5-HTTLPR的短等位基因倾向于降低血清素浓度，而G1222A的A等位基因则降低血清素和下丘脑泌素-1水平。血清素浓度因偏头痛的临床特征而异。5-HTTLPR、G1222A的基因型与血清素浓度之间的关系在偏头痛中可能受到干扰。似乎G29A与MA患者血清素调节的关联比MO患者更强，因此可能导致偏头痛的发病年龄较早。
