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Published in: The Journal of Headache and Pain 1/2015

Open Access 01-12-2016 | Research article

Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines

Authors: Sırma Geyik, Sercan Ergun, Samiye Kuzudişli, Figen Şensoy, Ebru Temiz, Erman Altunışık, Murat Korkmaz, Hasan Dağlı, Seval Kul, Aylin Akçalı, Ayşe Münife Neyal

Published in: The Journal of Headache and Pain | Issue 1/2015

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Abstract

Background

Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA).

Methods

One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed.

Results

Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (β = 0.508, p = 0.001).

Conclusion

Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.
Literature
2.
go back to reference Demarquay G, Mauguière F (2015) Central nervous system underpinnings of sensory hypersensitivity in migraine: insights from Neuroimaging and electrophysiological studies. Headache. doi:10.1111/head.12651 PubMed Demarquay G, Mauguière F (2015) Central nervous system underpinnings of sensory hypersensitivity in migraine: insights from Neuroimaging and electrophysiological studies. Headache. doi:10.​1111/​head.​12651 PubMed
6.
go back to reference Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J, Svensson DA, Nyholt DR, Martin NG, MacGregor AJ, Cherkas LF, Boomsma DI, Palotie A (2003) Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 6(5):422–431. doi:10.1375/136905203770326420 CrossRefPubMed Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J, Svensson DA, Nyholt DR, Martin NG, MacGregor AJ, Cherkas LF, Boomsma DI, Palotie A (2003) Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 6(5):422–431. doi:10.​1375/​1369052037703264​20 CrossRefPubMed
8.
go back to reference Lavecchia A, Cosconati S, Novellino E (2005) Architecture of the human urotensin II receptor: comparison of the binding domains of peptide and non-peptide urotensin II agonists. J Med Chem 48(7):2480–2492. doi:10.1021/jm049110x CrossRefPubMed Lavecchia A, Cosconati S, Novellino E (2005) Architecture of the human urotensin II receptor: comparison of the binding domains of peptide and non-peptide urotensin II agonists. J Med Chem 48(7):2480–2492. doi:10.​1021/​jm049110x CrossRefPubMed
9.
go back to reference Jégou S, Cartier D, Dubessy C, Gonzalez BJ, Chatenet D, Tostivint H, Scalbert E, LePrince J, Vaudry H, Lihrmann I (2006) Localization of the urotensin II receptor in the rat central nervous system. J Comp Neurol 495(1):21–36. doi:10.1002/cne.20845 CrossRefPubMed Jégou S, Cartier D, Dubessy C, Gonzalez BJ, Chatenet D, Tostivint H, Scalbert E, LePrince J, Vaudry H, Lihrmann I (2006) Localization of the urotensin II receptor in the rat central nervous system. J Comp Neurol 495(1):21–36. doi:10.​1002/​cne.​20845 CrossRefPubMed
11.
go back to reference MacLean MR, Alexander D, Stirrat A, Gallagher M, Douglas SA, Ohlstein EH, Morecroft I, Polland K (2000) Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol 130(2):201–204. doi:10.1038/sj.bjp.0703314 CrossRefPubMedPubMedCentral MacLean MR, Alexander D, Stirrat A, Gallagher M, Douglas SA, Ohlstein EH, Morecroft I, Polland K (2000) Contractile responses to human urotensin-II in rat and human pulmonary arteries: effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol 130(2):201–204. doi:10.​1038/​sj.​bjp.​0703314 CrossRefPubMedPubMedCentral
14.
go back to reference Huitron-Resendiz S, Kristensen MP, Sánchez-Alavez M, Clark SD, Grupke SL, Tyler C, Suzuki C, Nothacker HP, Civelli O, Criado JR, Henriksen SJ, Leonard CS, de Lecea L (2005) Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons. J Neurosci 25(23):5465–5474. doi:10.1523/JNEUROSCI.4501-04.2005 CrossRefPubMed Huitron-Resendiz S, Kristensen MP, Sánchez-Alavez M, Clark SD, Grupke SL, Tyler C, Suzuki C, Nothacker HP, Civelli O, Criado JR, Henriksen SJ, Leonard CS, de Lecea L (2005) Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons. J Neurosci 25(23):5465–5474. doi:10.​1523/​JNEUROSCI.​4501-04.​2005 CrossRefPubMed
17.
go back to reference Suzuki S, Wenyi Z, Hirai M, Hinokio Y, Suzuki C, Yamada T, Yoshizumi S, Suzuki M, Tanizawa Y, Matsutani A, Oka Y (2004) Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese. Peptides 25(10):1803–1808. doi:10.1016/j.peptides.2004.03.030 CrossRefPubMed Suzuki S, Wenyi Z, Hirai M, Hinokio Y, Suzuki C, Yamada T, Yoshizumi S, Suzuki M, Tanizawa Y, Matsutani A, Oka Y (2004) Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese. Peptides 25(10):1803–1808. doi:10.​1016/​j.​peptides.​2004.​03.​030 CrossRefPubMed
18.
19.
go back to reference Michaels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW (2010) Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 5(6):1003–1009. doi:10.2215/CJN.06870909 CrossRef Michaels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW (2010) Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 5(6):1003–1009. doi:10.​2215/​CJN.​06870909 CrossRef
23.
go back to reference Cernuda-Morollon E, Martinez-Camblor P, Ramon C, Larrosa D, Serrano-Pertierra E, Pascual J (2014) CGRP and VIP levels as predictors of efficacy of Onabotulinumtoxin type A in chronic migraine. Headache 54(6):987–995. doi:10.1111/head.12372 CrossRefPubMed Cernuda-Morollon E, Martinez-Camblor P, Ramon C, Larrosa D, Serrano-Pertierra E, Pascual J (2014) CGRP and VIP levels as predictors of efficacy of Onabotulinumtoxin type A in chronic migraine. Headache 54(6):987–995. doi:10.​1111/​head.​12372 CrossRefPubMed
31.
go back to reference Malik R, Winsvold B, Auffenberg E, Dichgans M, Freilinger T (2015) The migraine-stroke connection: A genetic perspective. Cephalalgia. Dec 9. 0333102415621055. [Epub ahead of print] Malik R, Winsvold B, Auffenberg E, Dichgans M, Freilinger T (2015) The migraine-stroke connection: A genetic perspective. Cephalalgia. Dec 9. 0333102415621055. [Epub ahead of print]
32.
go back to reference Tietjen EG (2007) Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia 27(8):981–987CrossRefPubMed Tietjen EG (2007) Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia 27(8):981–987CrossRefPubMed
33.
go back to reference Pezzini A, Del Zotto E, Giossi A, Volonghi I, Grassi M, Padovani A (2009) The migraine-ischemic stroke connection: potential pathogenic mechanisms. Curr Mol Med 9(2):215–26CrossRefPubMed Pezzini A, Del Zotto E, Giossi A, Volonghi I, Grassi M, Padovani A (2009) The migraine-ischemic stroke connection: potential pathogenic mechanisms. Curr Mol Med 9(2):215–26CrossRefPubMed
36.
go back to reference Wenyi Z, Suzuki S, Hirai M, Hinokio Y, Tanizawa Y, Matsutani A, Satoh J, Oka Y (2003) Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjects. Diabetologia 46(7):972–976CrossRefPubMed Wenyi Z, Suzuki S, Hirai M, Hinokio Y, Tanizawa Y, Matsutani A, Satoh J, Oka Y (2003) Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjects. Diabetologia 46(7):972–976CrossRefPubMed
37.
go back to reference Ong KL, Wong LY, Man YB, Leung RY, Song YQ, Lam KS, Cheung BM (2006) Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance. Peptides 27(7):1659–1667CrossRefPubMed Ong KL, Wong LY, Man YB, Leung RY, Song YQ, Lam KS, Cheung BM (2006) Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance. Peptides 27(7):1659–1667CrossRefPubMed
38.
go back to reference Oztuzcu S, Ulasli M, Pehlivan Y, Cevik MO, Cengiz B, Igci YZ, Okumuş S, Arslan A, Onat AM (2013) Thr21Met (T21M) but not Ser89Asn (S89N) polymorphisms of the urotensin-II (UTS-II) gene are associated with Behcet’s disease (BD). Peptides 42:97–100. doi:10.1016/j CrossRefPubMed Oztuzcu S, Ulasli M, Pehlivan Y, Cevik MO, Cengiz B, Igci YZ, Okumuş S, Arslan A, Onat AM (2013) Thr21Met (T21M) but not Ser89Asn (S89N) polymorphisms of the urotensin-II (UTS-II) gene are associated with Behcet’s disease (BD). Peptides 42:97–100. doi:10.​1016/​j CrossRefPubMed
39.
go back to reference Tobias Freilinger, Verneri Anttila, Boukje de Vries, Rainer Malik, Mikko Kallela, Gisela M Terwindt, Patricia Pozo-Rosich,Bendik Winsvold, Dale R Nyholt, Willebrordus P J van Oosterhout, Ville Artto, Unda Todt, Eija Hämäläinen, Jèssica Fernández-Morales, Mark A Louter, Mari A Kaunisto, Jean Schoenen, Olli Raitakari, Terho Lehtimäki, Marta Vila-Pueyo, Hartmut Göbel, Erich Wichmann, Cèlia Sintas, Andre G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Axel Heinze, Erling Tronvik, Cornelia M van Duijn, Jaakko Kaprio, Bru Cormand, Maija Wessman, Rune R Frants, Thomas eitinger, Bertram Müller-Myhsok, John-Anker Zwart, Markus Färkkilä, Alfons Macaya, Michel Derrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M J M van den Maagdenberg & International Headache Genetics Consortium (2012) Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nature Genetics 44:777–782. doi:10.1038/ng.2307 Tobias Freilinger, Verneri Anttila, Boukje de Vries, Rainer Malik, Mikko Kallela, Gisela M Terwindt, Patricia Pozo-Rosich,Bendik Winsvold, Dale R Nyholt, Willebrordus P J van Oosterhout, Ville Artto, Unda Todt, Eija Hämäläinen, Jèssica Fernández-Morales, Mark A Louter, Mari A Kaunisto, Jean Schoenen, Olli Raitakari, Terho Lehtimäki, Marta Vila-Pueyo, Hartmut Göbel, Erich Wichmann, Cèlia Sintas, Andre G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Axel Heinze, Erling Tronvik, Cornelia M van Duijn, Jaakko Kaprio, Bru Cormand, Maija Wessman, Rune R Frants, Thomas eitinger, Bertram Müller-Myhsok, John-Anker Zwart, Markus Färkkilä, Alfons Macaya, Michel Derrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M J M van den Maagdenberg & International Headache Genetics Consortium (2012) Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nature Genetics 44:777–782. doi:10.​1038/​ng.​2307
Metadata
Title
Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines
Authors
Sırma Geyik
Sercan Ergun
Samiye Kuzudişli
Figen Şensoy
Ebru Temiz
Erman Altunışık
Murat Korkmaz
Hasan Dağlı
Seval Kul
Aylin Akçalı
Ayşe Münife Neyal
Publication date
01-12-2016
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2015
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-016-0623-z

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