Association between dopamine receptor genes and migraine without aura in a Sardinian sample

Zompo, Maria Del; Cherchi, A.; Palmas, Maria Antonietta; Ponti, M.; Bocchetta, Alberto; Gl, Gessa; Piccardi, M.P.

doi:10.1212/wnl.51.3.781

Cited by 113 publications

(98 citation statements)

References 18 publications

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“…In this study, we analyzed the genes for D1, D2, D3 and D4 receptors. We found a positive association between the "dopaminergic" phenotype of migraine without aura and the D2 receptor gene [17]. Recently, we studied D5 in 100 trios and concluded that it was not involved in migraine pathogenesis in the study population [18].…”

Section: Genetic Studiesmentioning

confidence: 83%

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Role of dopaminergic system in migraine

et al. 2001

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IntroductionDespite recent advances, the pathogenesis of migraine is still unclear. The study of migraine pathophysiology includes the investigation of neurotransmitters and their potential role in the development of the attack. Scientific and clinical interest has focused on the role of 5-hydroxytryptamine (5-HT). However, the dopaminergic system also appears to play a major, still less recognized, role in migraine and dopamine (DA) can be considered the "second putative protagonist in headache" [1]. Several arguments suggest the involvement of DA in migraine pathophysiology [2,3].The dopaminergic system has a prominent role in motor and sensorial control, in modulating cognitive processes, and in the control of both prolactin and growth hormone secretion. Recently, a key role in the regulation of cerebral microcirculation has been demonstrated [4]. Based on their structure and pharmacological characteristics, five subtypes of DA receptors have been described: D1, D4 and D5 are Gs protein-coupled receptors, D2 is a Gi protein-coupled receptor, and the signal transducing system of D3 is not yet completely characterized.Evidence for hypersensitivity of the dopaminergic system in migraineThe theory that hypersensitivity of the DA system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Role of dopaminergic system in migraine Alessandra Cherchi Erminia Stochino Maria Paola Piccardi Maria Del ZompoAbstract The theory that hypersensitivity of dopamine (DA) system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Apomorphine, a selective and specific DA agonist, has a cerebral vasodilatatory effect and increases blood flow significantly in the middle cerebral artery in migraineurs. Processes from central DA neurons terminate in close contact with penetrating arterioles and cerebral capillaries in the cerebral cortex. This finding reaffirms the role of central neurogenic mechanisms in the regulation of the cerebral circulation and, we believe, further supports the major role of dopamine in the neurogenic mechanisms of migraine. Various studies have been carried out to verify the involvement of DA in migraine pathogenesis using molecular genetics as a tool. A positive association between the "dopaminergic" phenotype of migraine without aura and the D2 receptor gene has been found. To explain dopaminergic hypersensitivity in migraine without aura, we will study the genes encoding proteins involved in the signal transduction system.

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Section: Genetic Studiesmentioning

confidence: 83%

“…Another study was performed by our group [17], using a family-based method, in a randomized sample of 50 trios, each trio consisting of a subject affected by migraine without aura and his or her parents. In this study, we analyzed the genes for D1, D2, D3 and D4 receptors.…”

Section: Genetic Studiesmentioning

confidence: 99%

Role of dopaminergic system in migraine

et al. 2001

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“…However, the genetic evidence is murky, since positive studies of association with dopamine receptors genes, in particular DRD2, have been contradicted in other populations. NcoIC allele of the DRD2 gene was found associated with MA, and in particular with MA co-morbid with anxiety and depression, by Allelic association with migraine (increased Stin 2.10 allele) [40] No association or linkage with migraine [15,41] 5-HT2A (13q14-21) Allelic association (C allele) with aura but not with migraine [42] No [23] MtDNA deletion in 1 case with migraine stroke Shimomura et al (1995) [35] 11084 mtDNA mutation in 25% of 53 Japanese migraineurs Ojaimi et al (1998) [32] 4216 and 13708 LHON secondary mutations in juvenile stroke Majamaa et al (1997) [31] MELAS mutation in 6% of juvenile migraine stroke Majamaa et al (1998) [29] MtDNA U haplotype in migraine stroke Finnila et al (2001) [33] MtDNA U5 haplotype and tRNA mutations in migraine stroke Ohno et al (1998) [36] tRNA Glu and 12SrRNA mutations in matrilinear FHM Shimomura et al (1994) [37] tRNA Leu UUR mutation in cluster headache Odawara et al (1997) [38] mtDNA deletion in cluster headache Boles et al (1999) [34] 8.1 kb mtDNA deletion in cyclic vomiting syndrome Allelic association (NcoI allele) with MA co-morbid with [49] anxiety/depression Allelic association (allele 1) with yawning/nausea during MO attack [50] No allelic (NcoI allele) association with MA [51] No allelic association with MO/MA [52] No allelic association with migraine [41] …”

Section: Migraine and Dopamine Metabolism Genesmentioning

confidence: 99%

“…Allelic association with typical migraine [41] MA, migraine with aura; MO, migraine without aura; DBH, dopamine beta-hydroxylase Peroutka et al [48,49], and Del Zompo et al [50] found an association between DRD2 (but not DRD1 and DRD3) and MO in a sample of Sardinian families analysed by means of transmission dysequilibrium test: allele I of DRD2 was associated with yawning and nausea during the migraine attack, though not with migraine itself. Dichgans et al [51], however, questioned these DRD2 findings: in their own population no particular association of NcoI allele with MA was found; moreover they pointed out that the allele is not functional, meaning that the particular DNA transition results in the same aminoacid and protein and therefore does not change the function of the dopamine receptor.…”

Section: Comt Mao-a Dbhmentioning

confidence: 99%

The “typical” migraines: genetic studies and some practical considerations

2003

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"Typical" migraine as a complex disease: genetic epidemiology, twin and segregation analysis studies That migraine runs in families is an ancient observation. Familiarity however is not synonymous with heritability, especially given the wide prevalence of migraine and the possibility that familial occurrence is due to chance. In order to assess the heritability of migraine, e.g. the rate of variance attributable to genetic factors, the disease risk of relatives of migraine probands is determined and compared to that found in the general population. Several surveys indicated that first-and sometimes also seconddegree relatives of migraine probands show increased risk for migraine: a two-fold increased risk for migraine without aura (MO) and 1.4 for migraine with aura (MA) in the case of first-degree relatives of MO probands, and a 4-fold risk for MA in the case of first-degree relatives of MA probands [1]. An increased disease risk does not however prove heritability, since it may result from shared environmental factors. It is therefore interesting to note that at least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives compared to spouses of migraine probands, who presumably share environmental factors at least for some time in their lives. Notably however, the relative risk for spouses was increased compared to the general population, which implies some degree of assorted mating or shared environmental influences [1]. Studies of heritability performed according to disease risk comparisons came to high rates of genetic determination, e.g. 60%-80% for MO and MA [2].Better ways of analysing heritability of migraine are studies of monozygotic versus dizygotic twins, especially when reared-together and reared-apart (adopted) identical twins are considered. Several twin studies have been performed in migraine Pasquale Montagna Pietro Cortelli Mirella MochiAbstract Epidemiological genetic, family and twin studies show that the typical migraines carry a substantial genetic risk; they are currently conceptualized as complex genetic diseases. Several genetic association and linkage studies have been performed in the typical migraines. Candidate gene studies based on "a priori" pathogenic models of migraine (migraine as a calcium channelopathy; a mitochondrial DNA disorder; a disorder in the metabolism of serotonin or dopamine; in vascular risk factors or in the inflammation cascade; etc.) did not result in uniformely accepted findings. Linkage and genome wide scans gave evidence for several genetic susceptibility loci, still however in need of confirmation. Careful dissection of the clinical phenotypes and trigger factors shall greatly help future efforts in the quest for the genetic basis of the typical migraines.

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“…The pathogenesis of migraine is not yet fully understood but both neural and vascular mechanisms are known to be involved [3,4]; moreover, an altered monoaminergic neurotransmission has also been implicated, particularly of serotonergic and, more recently, dopaminergic systems [5]. In this regard, some authors have reported an association between migraine and the gene of D2 dopaminergic receptors [6,7].…”

Section: Introductionmentioning

confidence: 99%

Association study between clinical response to rizatriptan and some candidate genes

et al. 2007

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The aim of this study was to test genetic differences in the clinical response to rizatriptan in patients affected by migraine without aura. These genetic differences could be explained by various genes, the HTR1B, encoding the 5-HT1 receptor subtype, MAO-A gene that encodes the monoamino-oxidase, the main metabolic enzyme of this triptan, SLC6A4 (gene encoding the serotonin transporter) and DRD2 (gene encoding the D2 receptor), both involved in the pathogenesis of migraine. Fifty unrelated patients affected by migraine without aura (IHS) were included. Patients were divided into two groups (responders and non-responders) according to clinical response. Thirty-one out of fifty patients responded to rizatriptan. A significant difference among the two groups was observed in both allele (p=0.02) and genotype distribution (p=0.03) of DRD2/NcoI. The significant association with the DRD2/NcoI polymorphism in responders suggested that the DRD2/NcoI C allele may be considered a susceptibility factor heralding a good response to rizatriptan.

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Association between dopamine receptor genes and migraine without aura in a Sardinian sample

Abstract: Our data suggest that a genetic approach could be useful in providing molecular support to the hypothesis that hypersensitivity of the dopaminergic system may represent the pathophysiologic basis of migraine, at least in a subgroup of patients.

Cited by 113 publications

References 18 publications

Role of dopaminergic system in migraine

Role of dopaminergic system in migraine

The “typical” migraines: genetic studies and some practical considerations

Association study between clinical response to rizatriptan and some candidate genes

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