【作者】 张现伟；

【导师】 吴宣富；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2008， 硕士

【摘要】 背景:偏头痛是一种常见的原发性头痛,以反复发作的搏动性头痛伴恶心呕吐、畏光畏声为特点。其病因及发病机制至今未明,但一般认为与遗传和环境等因素相关。家族性偏瘫型偏头痛(familial hemiplegic migraine,FHM)是一种罕见的常染色体显性遗传病。迄今为止,在FHM家系中共鉴定出3种基因突变——CACNA1A基因、ATP1A2基因和SCN1A基因。近年来,分子遗传学研究成为偏头痛发病机制研究的热点。5-羟色胺(5-hydroxytryptamine,5-HT)相关基因在偏头痛发病中的作用已逐渐明确,其中5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT)基因作为偏头痛的候选基因,在国外进行了较多的研究,而国内尚未见报道。该基因多态性与中医证型的研究国内有少量报道,但与偏头痛证型的研究尚未见报道。另外,祖国医学对偏头痛病因病机的认识,历代医家论述颇多,一般认为与风、火、痰、瘀、虚等有关。但偏头痛的辨证分型尚缺乏统一标准,且关于偏头痛患者辨证分型分布情况的观察研究也较少。目的:观察偏头痛患者中医证型的分布情况,以指导临床;研究5-HTT基因多态性频率分布与偏头痛中医证型、偏头痛及其临床特征的相关性,探求该基因多态性在偏头痛发病中的作用。方法:收集40例偏头痛患者(实验组)和40例性别、年龄相匹配的健康成人(对照组),将40例偏头痛患者根据家族史的有无,分为2组,即有家族史组和无家族史组,观察两组患者临床特征的差异。同时对两组患者进行辨证分型,分析两组患者的中医证型分布特点;采集40例实验组和40例对照组的肘静脉血,通过DNA—PCR扩增及琼脂糖凝胶电泳等分子生物学技术,观察5-HTT基因多态性的基因型和等位基因频率在两组中的分布特点,及其与偏头痛的中医证型和临床特征的相关性,从而探讨5-HTT基因多态性与偏头痛的关系。结果:有家族史患者和无家族史者比较,有家族史患者的病程较长(7.04±5.84,3.56±2.77,P＜0.05)。两组患者在发病年龄、发作频率、持续时间、严重程度及中医证型分布方面无明显差异(P均大于0.05)。对所有的偏头痛患者进行辨证分型,发现瘀阻脑络型最多见(19例,占47.5%);对5-HTT基因两个多态性的研究发现,5-HTT基因多态性的基因型和等位基因频率在实验组和对照组中的分布无统计学差异P＞0.05),在偏头痛患者各临床特征中的分布也无统计学差异(P＞0.05)。但在其与偏头痛证型的相关性研究中,发现5-HTTLPR的S等位基因频率在瘀阻脑络型患者中分布较高(X~2=4.125,P=0.042)。结论:在偏头痛患者的证型分布中,瘀阻脑络型最常见,说明瘀血是偏头痛发病的主要病理因素。5-HTTLPR多态性基因型和等位基因频率分布在实验组和对照组间无显著差异,但该多态性的S等位基因频率在瘀阻脑络型中的分布较高,可能该多态性与偏头痛瘀阻脑络型的发病相关。5-HTT基因VNTRs多态性的基因型和等位基因频率分布在实验组和对照组间无显著差异,提示该多态性可能不是汉族人群偏头痛患者的危险因素。5-HTT基因的两个多态性在偏头痛的各临床特征间无差异,可能与偏头痛的各临床特征无相关性。但由于本研究样本量较小,这一结论尚有待大样本研究来证实。更多还原

【Abstract】 Background:Migraine is a common type of primary headache, Characteristics of the disorder are severe episodes of headache, throbbing headache with nausea, vomiting and sensory sensitivity to light and sound. Its etiology and Pathogenetic pathways is still unclear. However, it’ s usually thought to be associated with genetics and environment. Familial hemiplegic migraine(FHM) is a rare autosomal dominant disease. FHM mutations so far were identified including those in CACNA1A, ATP1A2 and SCN1A genes. Recently, molecular genetics studies have become a topic of general interest on the pathogenesy of migraine. There is evidence to suggest that 5-hydroxytryptamine(5-HT) -related genes participate in the pathogenesis of migraine. As a candidate gene affecting migraine, a great many of researches on 5-HT transporter (5-HTT) gene have been carried out in other countries, but no reports in China. In addition, although many views on etiology and pathogenesy of TCM, generally speaking, it concerns with wind, fire, phlegm, blood stasis and deficiency. But until now, there isn’t definited and unanimous standard in treatment by differentiation of symptoms and signs. There are a few studies on the distributions in migraineur of differentiation of symptoms and signs, else.Objective:To investigate the distributions in migraineur of differentiation of symptoms and signs; Two polymorphisms of 5-HTT gene were analyzed to assess whether theses variants are associated with migraine.Methods:40 migraineurs and 40 controls were included in this study. According to migraineurs with family history or not, 40 patients were divided into two groups. Observe the difference of clinical features between two groups. Simultaneously, differentiation of symptoms and signs were carried out to observe the distributions of the two groups; Collect 40 migraineurs’ and controls’ vein blood. Through DNA-PCR amplification and agarose gel electro- phoresis, we observed the genotype frequencies and allele distributions of 5-HTT gene polymorphisms in migraineurs and controls, and investigated the genotype and allele frequencies in differentiation of symptoms and signs.Results: Comparing with migraineurs without family history, the course of disease was longer in migraineurs with family history (7.04±5.84, 3.56±2.77, P<0.05). There was no significant association in the age at onset, frequencies of attack, duration, clinical severity between migraineurs with and without family history (P>0.05). However, blood stasis blocked meridian was the commonest in four types of symptom of TCM(19/47.5%). There was no significant difference in genotype or allele frequencies distributions of 5-HTTLPR and VNTR polymorphisms between migraineurs and controls (P>0.05). There was also no significant association between clinical features of migraine and genotype of 5-HTT gene polymorphisms (P>0.05). Although there wasn’t any different distributions between 5-HTTLPR genotype frequencies and differentiation of symptoms and signs, 5-HTTLPR polymorphism S allele is more frequent in blood stasis blocked meridian (x~2=4.125, P=0.042) .Conclusions: The blood stasis blocked meridian is the commonest in four types of symptom of TCM. These indicate that blood stasis is a main pathological factor which leads to migraine attack. Although there is no significant difference in genotype or allele frequencies distributions of 5-HTTLPR polymorphisms between migraineurs and controls, S allele of this polymorphism is more frequent in blood stasis blocked meridian. It is probable that 5-HTTLPR participates in the pathogenesis of blood stasis blocked meridian. There is no significant difference in genotype or allele frequencies distributions of VNTRs polymorphisms between migraineurs and controls, it is possible that VNTRs polymorphism is not a risk factor in migraineurs in Han population. There is no difference in two polymorphisms of 5-HTT gene and clinical features of migraine, perhaps no association exists between two polymorphisms and all clinical features of migraine. Owing to the small sample in this study, further study will be needed in large sample to establish the conclusions in future.更多还原