<scp><i>KCNK</i></scp><i>18</i> (<scp>TRESK</scp>) Genetic Variants in <scp>I</scp>talian Patients With Migraine

Rainero, Innocenzo; Rubino, Elisa; Gallone, Salvatore; Zavarise, Paola; Carli, Daniela; Boschi, Silvia; Fenoglio, Pierpaola; Savi, L; Gentile, Salvatore; Benna, Paolo; Pinessi, Lorenzo; Volta, Giorgio Dalla

doi:10.1111/head.12439

Cited by 17 publications

(16 citation statements)

References 33 publications

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“…In the present study, we found that polymorphism c.28A>G, as well as mutation c.328T>C of KCNK18 gene, occurred with similar frequency in the control group and migraine patients. It corresponds with previous studies of c.28A>G [ 13 , 20 ] and c.328T>C [ 13 , 37 ] variants. Whereas, Rainero et al [ 20 ] found the mutation only in migraine patients, both MA and MO.…”

Section: Discussionsupporting

confidence: 92%

“…It corresponds with previous studies of c.28A>G [ 13 , 20 ] and c.328T>C [ 13 , 37 ] variants. Whereas, Rainero et al [ 20 ] found the mutation only in migraine patients, both MA and MO. It was also previously found in Polish patients with MA [ 10 ].…”

Section: Discussionsupporting

confidence: 92%

“…For the combined analyses of c.28A>G and c.328T>C variants in KCNK18 , a total sample of 1164 migraine patients and 975 controls was used. It was obtained from our case-control group (170 migraine patients and 173 controls) with the prior case-control studies: the two case-control studies of multicenter collaboration by Lafrenière et al [ 13 ] (A: 110 migraine patients among which 13 of French-Canadian origin, 44 of Canadian, and 53 of Portuguese origin and 80 controls of Canadian origin; B: 459 Australian migraine patients and 475 Australian controls) and the Italian study by Rainero et al [ 20 ] (425 migraine patients and 247 controls).…”

Section: Methodsmentioning

confidence: 99%

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Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Kowalska

Prendecki

Kapelusiak-Pielok

et al. 2020

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Background: Migraine is a polygenetic disease, considered as a channelopathy. The dysregulation of ion functioning due to genetic changes may activate the trigeminovascular system and induce migraine attack both migraine with aura (MA) and without aura (MO). Objectives: The aim of the study was to analyze the following variants of genes encoding ion channels and associated protein: c.3199G>A SCN1A, c.56G>A SCN2A, c.28A>G and c.328T>C KCNK18, c.3053A>G TRPA1, c.31-1811C>T STX1A in migraine patients. Patients and Methods: The study included 170 migraine patients and 173 controls. HRMA and Sanger sequencing were used for genotyping. Meta-analysis was performed for c.28A>G, c.328T>C KCNK18, and c.31-1811C>T STX1A. Patients and Methods: The study included 170 migraine patients and 173 controls. HRMA and Sanger sequencing were used for genotyping. Meta-analysis was performed for c.28A>G, c.328T>C KCNK18, and c.31-1811C>T STX1A. Results: AA genotype of c.56G>A SCN2A was found only in migraine patients. Patients with c.328T>C KCNK18 mutation had an increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of KCNK18 had higher attack frequency than those with AA/TT (p<0.05). T allele of c.31-1811C>T STX1A was more frequent in MA patients than MO (p<0.05). The c.3053A>G TRPA1 polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T STX1A and c.3199G>A SCN1A before the age of 10 (p<0.01). Meta-analysis showed a significant association of c.31-1811C>T STX1A polymorphism with migraine overall (OR=1.22, p=0.0086), MA, and MO. No association was found for c.28A>G KCNK18, c.328T>C KCNK18, and migraine overall. Conclusions: Changes in genes encoding ion channels or proteins regulating their functioning may increase the risk of migraines and correlate with clinical features of disease, e.g. age of onset and attack frequency.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

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Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Kowalska

Prendecki

Kapelusiak-Pielok

et al. 2020

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“…This mutation has already been well characterized and shown to be migraine-related but not to influence the activity of the TRESK K2P potassium channel encoded by KSNK18 [ 24 ]. Other studies on this variant also showed relationship to migraine with typical aura [ 25 ]. Accordingly, we found the KCNK18 mutation in a patient with migraine without aura.…”

Section: Discussionmentioning

confidence: 83%

Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes

et al. 2016

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Background and aimMigraine is the most common neurological disorder, affecting approximately 12 % of the adult population worldwide, caused by both environmental and genetic factors. Three causative genes have been identified in familial hemiplegic migraine (FHM) families: CACNA1A, ATP1A2, and SCNA1A. Recently, several mutations in KCNK18 have also been found as causative factors in migraine development. The aim of our study was to identify the genetic background of migraine in the Polish population.Material and methodsSixty patients with migraine without aura (MO) or with different types of migraine with aura (MA), including sporadic hemiplegic, familial hemiplegic, and probable familial hemiplegic, were screened for mutations in the four genes previously linked with different types of migraine (ATP1A2, CACNA1A, SCN1A, and KCNK18).ResultsTwo missense mutations were found. One novel mutation in SCN1A, encoding α subunit of sodium channel, causing amino acid change M1500V localized to a region encoding inactivation loop between transmembrane domains III and IV of the channel, was detected in a female FHM patient. The M1500V mutation was absent in a group of 62 controls, as well as in the ExAC database. The second, already known missense mutation S231P in KCNK18 was found in a female MA patient. Additionally, a novel intronic polymorphism possibly affecting alternative splicing of SCN1A, at chr2:16685249, g.77659T>C, and c.4581+32A>G, located between exons 24 and 25, in a region encoding the inactivation loop of the sodium channel was found in a female MO patient. No mutations in ATP1A2 or CACNA1A were found in the study group.ConclusionsThe presence of SCN1A mutations and absence of mutations in ATP1A2 or CACNA1A suggest that the Polish patients represent FHM type 3. On the other hand, the presence of KCNK18 mutation indicated another FHM subtype. It could be speculated that contrary to other European populations, the genetic basis of migraine in the Polish population involves mutations in genes not included in the study. Next-generation sequencing methods should be implemented to identify other migraine-associated variants.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-015-0057-8) contains supplementary material, which is available to authorized users.

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“…Surprisingly, other mutations that inactivate TRESK were not correlated with migraine [57,58]. A number of KCNK18 missense variants (R10G, A34V, C110R, S231P, A233V) were also identified in unrelated sporadic migraine and control cohorts [20], as well as in Italian migraine patients [59]. Some variants (R10G, S231P, and A233V) did not appear to significantly affect TRESK current, [57] but, unexpectedly, the C110R variant, despite producing a complete loss of TRESK function, did not show an association with the disease, as it was expressed both in control and sporadic migraine cohorts.…”

Section: Tresk and Migrainementioning

confidence: 99%

The Background K+ Channel TRESK in Sensory Physiology and Pain

Andrés‐Bilbé

Castellanos

Pujol-Coma

et al. 2020

IJMS

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TRESK belongs to the K2P family of potassium channels, also known as background or leak potassium channels due to their biophysical properties and their role regulating membrane potential of cells. Several studies to date have highlighted the role of TRESK in regulating the excitability of specific subtypes of sensory neurons. These findings suggest TRESK could be involved in pain sensitivity. Here, we review the different evidence available that involves the channel in pain and sensory perception, from studies knocking out the channel or overexpressing it to identified mutations that link the channel to migraine pain. In addition, the therapeutic possibilities are discussed, as targeting the channel seems an interesting therapeutic approach to reduce nociceptor activation and to decrease pain.

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KCNK18 (TRESK) Genetic Variants in Italian Patients With Migraine

Abstract: Our study shows the presence of several KCNK18 gene mutations in both migraine with aura and migraine without aura. However, the precise role of this gene in migraine predisposition deserves further studies.

Cited by 17 publications

References 33 publications

Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes

The Background K+ Channel TRESK in Sensory Physiology and Pain

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