Aims
RAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.
Methods
In a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).
Results
The distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.
Conclusion
Current results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development.
Microscopic basicity of some ketenimine derivatives 1-12 and their isomers/tautomers, bearing an unsaturated ring, has been studied in the present work. Isomerization process for some ketenimine derivatives and their protonated forms was also investigated by density functional theory (DFT) calculations. The protonation study in gas phase was performed by the DFT-B3LYP/6-311+G(d,p) computational method. The results show that all the proposed ketenimines (less stable than their isomers/tautomers) have proton affinity (PA) values that are more than at least 20 kJ mol À1 greater than the PA of 1,8-bis-(dimethylamino)naphthalene. The primary strategy in this study for designing new exceptionally rare ketenimine forms possessing strong basicity is to link structurally an unsaturated ring to the molecular framework and to build conjugated systems, for which the positive charge of the conjugate acids is delocalized through resonance. PA values are enhanced by placing electron-donating substituents on the unsaturated rings, stabilizing the conjugate acid. Two indices of aromaticity, the nucleus-independent chemical shift and the harmonic oscillator model of aromaticity associated with the unsaturated ring, were calculated and compared for neutral and protonated forms. Natural bond orbital (NBO)-Wiberg bond orders, highest occupied molecular orbital (HOMO), and molecular electrostatic potential investigations were also applied to explain the π-type interaction of the unsaturated ring with the ketenimine unit.
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