A280V Polymorphism in the Histamine H3 Receptor as a Risk Factor for Migraine

Millán‐Guerrero, Rebeca O.; Baltazar-Rodríguez, Luz M.; Cárdenas-Rojas, Martha I.; Ramírez-Flores, Mario; Isaís-Millán, Sara; Delgado‐Enciso, Iván; Caballero-Hoyos, Ramiro; Trujillo-Hernández, Benjamı́n

doi:10.1016/j.arcmed.2011.01.009

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…71415161718 We found that the CC genotype of rs4379368 and the TT genotype of rs10504861 may increase the risk of experiencing migraine with aura, and that the CC genotype of rs12134493 may reduce the susceptibility to migraine without aura. These findings and those of our previous study suggest that there are genetic differences in migraine susceptibility between the She and Han populations, and they raise the possibility that ethnicity differences across other populations can impact migraine.…”

Section: Discussionmentioning

confidence: 83%

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Lin

Chen

et al. 2017

J Clin Neurol

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Background and PurposeFive single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population.MethodsThis was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction—restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients.ResultsThe frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05).ConclusionsOur findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.

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Section: Discussionmentioning

confidence: 83%

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Lin

Chen

et al. 2017

J Clin Neurol

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“…The G293D substitution in H 3 R is analogous to the amino acid substitutions recently identified within the third IC domain of H 1 R underlying Bphs , a shared immunopathology disease gene controlling Bordetella pertussis -induced sensitivity to histamine, EAE, and autoimmune orchitis [28], [29], [30]. Importantly, a A280V missense mutation within the third IC loop of the human H 3 R gene has been reported in multiple system atrophy (Shy-Drager Syndrome), a rare neurodegenerative disease [31] and as a risk factor for migraine [32].…”

Section: Resultsmentioning

confidence: 94%

Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

et al. 2013

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Histamine H3 receptor (Hrh3/H3R) is primarily expressed by neurons in the central nervous system (CNS) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor. Previously, we identified an H3R-mediated central component in susceptibility to experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS), related to neurogenic control of blood brain barrier permeability and peripheral T cell effector responses. Furthermore, we identified Hrh3 as a positional candidate for the EAE susceptibility locus Eae8. Here, we characterize Hrh3 polymorphisms between EAE-susceptible and resistant SJL and B10.S mice, respectively, and show that Hrh3 isoform expression in the CNS is differentially regulated by acute peripheral inflammatory stimuli in an allele-specific fashion. Next, we show that Hrh3 is not expressed in any subpopulations of the immune compartment, and that secondary lymphoid tissue is anatomically poised to be regulated by central H3R signaling. Accordingly, using transcriptome analysis, we show that, inflammatory stimuli elicit unique transcriptional profiles in the lymph nodes of H3RKO mice compared to WT mice, which is indicative of negative regulation of peripheral immune responses by central H3R signaling. These results further support a functional link between the neurogenic control of T cell responses and susceptibility to CNS autoimmune disease coincident with acute and/or chronic peripheral inflammation. Pharmacological targeting of H3R may therefore be useful in preventing the development and formation of new lesions in MS, thereby limiting disease progression.

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“…This study originated from reports that the A280V mutation may be involved in the pathophysiology of two neurological disorders, the Shy–Drager syndrome (Wiedemann et al ., ) and migraine (Millán‐Guerrero et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Further, a recent report by Millán‐Guerrero et al . () indicated that in a Mexican population (147 cases and 186 controls) the A280V mutation was associated with increased risk of migraine.…”

Section: Introductionmentioning

confidence: 99%

A single‐point mutation (Ala280Val) in the third intracellular loop alters the signalling properties of the human histamine H₃ receptor stably expressed in CHO‐K1 cells

Flores-Clemente¹,

Osorio-Espinoza²,

Escamilla-Sánchez³

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEAn alanine to valine exchange at amino acid position 280 (A280V) in the third intracellular loop of the human histamine H3 receptor was first identified in a patient suffering from Shy-Drager syndrome and later reported as a risk factor for migraine. Here, we have compared the pharmacological and signalling properties of wild-type (hH3RWT) and A280V mutant (hH3RA280V) receptors stably expressed in CHO-K1 cells. EXPERIMENTAL APPROACHThe hH3RA280V cDNA was created by overlapping extension PCR amplification. Receptor expression and affinity were assessed by radioligand (N-α-[methyl- KEY RESULTSBoth receptors were expressed at similar levels with no significant differences in their affinities for H3 receptor ligands. Upon activation the hH3RWT was significantly more efficacious to inhibit forskolin-induced cAMP accumulation and to stimulate [ 35 S]-GTPγS binding, with no difference in pEC50 estimates. The hH3RWT was also more efficacious to stimulate ERK1/2 phosphorylation, but this difference was not significant. The inverse agonist ciproxifan was more efficacious at hH3RWT to reduce [ 35 S]-GTPγS binding but, for both receptors, failed to enhance forskolin-induced cAMP accumulation. CONCLUSIONS AND IMPLICATIONSThe A280V mutation reduces the signalling efficacy of the human H3 receptor. This effect may be relevant to the pathophysiology of disorders associated with the mutation.

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A280V Polymorphism in the Histamine H3 Receptor as a Risk Factor for Migraine

Cited by 15 publications

References 32 publications

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

A single‐point mutation (Ala280Val) in the third intracellular loop alters the signalling properties of the human histamine H₃ receptor stably expressed in CHO‐K1 cells

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A280V Polymorphism in the Histamine H3 Receptor as a Risk Factor for Migraine

Cited by 15 publications

References 32 publications

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Migraine Susceptibility Genes in Han Chinese of Fujian Province

Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

A single‐point mutation (Ala280Val) in the third intracellular loop alters the signalling properties of the human histamine H3 receptor stably expressed in CHO‐K1 cells

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A single‐point mutation (Ala280Val) in the third intracellular loop alters the signalling properties of the human histamine H₃ receptor stably expressed in CHO‐K1 cells