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

Abstract

BackgroundUrotensin-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).MethodsOne 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.ResultsPlasma 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).ConclusionOur 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.

Lack of association between urotensin-II (UTS2) gene polymorphisms (Thr21Met and Ser89Asn) and migraine

“…Our results indicate that the common genetic variation in the UTS2 gene unlikely plays a role in the development of migraine. However, these results are not in agreement with the findings reported by Geyik et al [13] who found that Thr21Met polymorphism was associated with the risk for migraine. Several factors could have contributed to the disparate results.…”

“…Several factors could have contributed to the disparate results. First, although their study was conducted at the same university as ours, Geyik et al [13] did not specifically indicate the ethnic background of their study population. In our study, all participants were Caucasians and of Turkish origin.…”

“…In our study, all participants were Caucasians and of Turkish origin. Another difference is that Geyik et al [13] only included patients with MA, while in our study, both MA and MO patients were investigated. The effect of Thr21Met and Ser89Asn polymorphisms on the structure, function, and plasma levels of U-II is still unclear, and requires further studies.…”

“…Recent GWA studies identified the 1p36 region as one of the susceptibility Lack of association between urotensin-II (UTS2) gene polymorphisms (Thr21Met and Ser89Asn) and migraine loci for migraine [8,12]. Moreover, a study on Turkish patients showed that UTS2 Thr21Met polymorphism was associated with the risk of migraine, but not UTS2 Ser89Asn polymorphism [13]. The aim of this study was to further investigate the association between the two UTS2 polymorphisms and migraine in a Turkish population.…”

The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory

“…Lipid peroxides are oxidation products and thus a biomarker of oxidative stress . The reason for higher levels interictally in migraineurs is unclear but may reflect lower activity of certain antioxidant enzymes, and/or increased activity of oxidant‐generating vasoconstrictors such as angiotensin, endothelin‐1, or urotensin‐2 . Alternatively, the source may be cortical hyperexcitablity, perhaps resulting in excessive oxidant production as a byproduct of the high metabolic rate .…”