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Genetics of Migraine - Is There Any Progress? Journal of Neurology & Stroke Genetics of Migraine - Is There any Progress? Abstract Review Article Nowadays migraine ranks 9th in the list of leading causes of disability among Volume 7 Issue 4 - 2017 population. In Russia migraine prevalence is two times higher than the world one-century history of studying migraine, science until now cannot explain many index and inflicts a considerable damage on the state economy. Despite almost – the therapy of patients with migraine is not sufficiently effective. Today one cases of attack occurrence. It causes difficulties both for diagnosis and treatment of the investigation directions is searching of migraine biomarkers confirming diagnosis. In this review we attempted to generalize the results of available works 1Faculty of Biology of Lomonosov Moscow State University, Keywords:targeted at searching genetic markers of migraine. Russia 2University diagnostic laboratory, Russia Migraine; Gene; Polymorphism 3University Headache Clinic, Russia 4Department of Neuroscience, I.M.Sechenov First Moscow State Medical University, Russia Introduction 5Centre of Theoretical Problems of Physico-Chemical Pharmacology, Russia 6I.I. Mechnikov Research Institute for Vaccines and Sera RAMS, Russia Migraine is now one of the leading causes of disability (ranks 7Department of neurology and neurosurgery, I.M. Sechenov 9th according to the WHO), comparable to such diseases as First Moscow State Medical University, Russia cancer, diabetes, cardiovascular diseases and others. In the female *Corresponding author: prevalencepopulation, inmigraine-related the world for 1 disability year in the ratio adult promotes population this disease ranges to 3rd place. According to epidemiological studies, migraine Eugene Klimov, Faculty of Biology of Lomonosov Moscow State University, Russia, Email: on average from 10.2% [1] to 14.7 % [2]. In Russia, migraine Received: | Published: prevalence exceeds world figures almost 1.5-2 fold, being 20.3%, March 18, 2017 September 19, 2017 and annual indirect costs (days lost due to disability) related to primary headaches total US $22.8 billion (1.75% of Russia’s gross domestic product) [3]. Thus, migraine is not only a medical, but alsoUntil a significant now, the economic diagnosis problem. of “migraine” is exclusively clinical, more often than the population in general; if both parents have and any diagnostic tests are aimed only at excluding other migraine, the risk that their offsprings will have this disease reaches 60-90% (vs. 11% in the control group), and the leading role belongs to the mother: in this case the risk of disease in causes of headache [4]. There are also problems with migraine childrenLong-term is 72%. studies have demonstrated familial aggregation of treatment and although both traditional analgesics and specific migraine symptoms, and in some cases a positive family history anti-migraine products are available in the market, treatment of migraine patients is still not sufficiently effective. For example, for migraine. Studies of monozygotic and dizygotic twins also specific anti-migraine agents (triptans) help control only two out (presence of the disease in family history) is a diagnostic criterion of three attacks, and migraine prevention products are considered the development of migraine: in monozygotic twins with migraine, effective, if they reduce the frequency of attacks by 50% or more. demonstrated the presence of a significant genetic component in The chronification of migraine attacks and the development of chronic daily headaches, occurring in 1% of patients per year pairsconcordance of twins value showed is 1.5-2 that timesgenetics higher and than environmental in dizygotic factors twins visiting[5], are specializeda significant headache clinical problem.centers are However, resistant about to standard 10% of (for MWOA and MWA) [8,9]. A large study involving about 30,000 migraine patients in the population and 40-60% of patients Studies of twins who grew up together or separately showed that generalcontribute environmental almost equally factors to the play development a secondary ofrole migraine [11,12]. [10]. therapy [6]. Treatment of such patients is the most expensive. diagnosis, instead of refuting other diagnoses, is the principal Thus, searching for migraine biomarkers that confirm such Differences in migraine prevalence between populations also vector in this scientific field. In this review, we attempted to may serve as an indirect evidence of the genetic basis of migraine summarize the available information about studies aimed at pathogenesis; such differences may be due to the differences in Discussionsearching for genetic markers of migraine. auraallele is frequencies stronger than between that in migraine populations. without According aura. Some to authorsforeign researchers [13,14], the genetic component in migraine with Inheritance of migraine define migraine as a polygenic multiple-factor disease [15,16]. of migraine [7]. Relatives of such patients have migraine much stimuliCurrently, of thethere nervous is a belief and vascularthat it is systems. not the disease itself that is Hereditary factors play an important role in the development inherited, but rather a predisposition to respond to external Submit Manuscript | http://medcraveonline.com J Neurol Stroke 2017, 7(4): 00245 Copyright: Genetics of Migraine - Is There any Progress? ©2017 Klimov et al. 2/9 Monogenic migraine syndromes This section presents rare neurological disorders, in which cerebral edema and white matter lesions; and premature death. Additional symptoms, such as migraine and Raynaud’s syndrome, are observed in more than a half of patients and occur almost ten maymigraine help attacks identify are a andpart ofunderstand a broader clinicalthe pathophysiological spectrum and can yearsPatients before with other the symptoms familial advanced[25-28]. sleep-phase syndrome mechanismsbe regarded asof amigraine. monogenic subtype of migraine. These subtypes (FASPS) CADASIL-syndrome: mutations have in the serious CSNK1D disturbances of the sleep-wake cycle and other circadian rhythms. The disease is caused by missense (Cerebral Autosomal Dominant gene encoding Iδ (CK1δ)CSNK1D casein mutations kinase Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) that is involved in the phosphorylation of Per2 circadian rhythm - a “cerebral autosomal dominant arteriopathy with subcortical protein [29-31]. In two independent families, hyperintensity,infarcts and leukoencephalopathy”, seizures, cognitive decline, characterized depression by andrecurrent other were observed in 9 of 11 patients with the familial advanced subcortical ischemic strokes with severe white matter sleep-phase syndrome and migraine with aura [29]. ScreeningCSNK1D with aura, is a characteristic peculiarity of more than a third of two families with migraine with aura and FASPS identified ofpsychoneurological patients, which occurssymptoms. at least Migraine, one decadein particular prior migraineto other (Csnk1d)two missense mutation mutations a have (c.44T> lower thresholdA and c.46H> for corticalR) in the spreading gene, which lead decreased enzyme levels [30]. Mice with T44A symptoms [17]. CADASIL is caused by mutations in the NOTCH3 depression, accompanied by increased spontaneous and induced gene that encodes the NOTCH3 receptor and plays a key role in activationCOL4A1-related of the calcium syndromes: signaling Thepathway COL4A1 in astrocytes gene [29].encodes the functioningsignaling pathway of smooth that muscle regulates cells the that development make up small of arteries vessels and arterioles in the brain [18]. Mutations lead to dysfunction of may lead to several autosomal dominant disorders with overlappingalpha-1 subunit characteristics, of type IV including collagen. perinatal Mutations hemorrhage in this genewith during embryogenesis and supports the structural/functional elimination,stability of blood which vessels leads to in the adults formation [19,20]. of granularA specific osmiophilic feature of CADASIL is the accumulation of NOTCH3 receptor due to its slow Theporencephalia association [32-35], of COLA4A1 and smallmutations vessel with disease, migraine which is notresult quite in cell adhesion and cell death, as well as in the transformation of hemorrhage and hemiparesis in childhood or adulthood [36]. deposits, and this affects small blood vessels and results in reduced COLA4A1 reliable and may be a random discovery, despite the fact that 10 insmooth the death muscle of cells smooth in the muscle middle cells layer in and the in vesselsfibrosis and[21]. in Thus, the out of 52 mutation carriers have confirmed migraines Familial and sporadic hemiplegic migraine (FHM) is degenerationCADASIL may of be the caused structure by vascular of vessels. dysfunction, which results (with or without aura) [35]. Mitochondrial encephalopathy, lactic acidosis, and stroke- like episodes (MELAS): characterized by migraine attacks combined with transient several mitochondrial genes, most frequently in the MTTL1 gene triggers;unilateral the motor same medicinalweakness. products Aura, headaches are used for and treatment associated and This disease is caused by mutations in symptoms are identical, and attacks can be caused by similar encoding the mitochondrial tRNA for leucine (nucleotide A to andprevention. migraine In are 75% more of FHMcommon patients, in women, hemiplegic and migraineepisodes ratesmay nucleotide G transition in position 3243), and is characterized alternate with migraine
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