A Study On The Relationship Between 5-hydroxytryptamine Transporter Gene Polymorphism And Migraine

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.