Molecular genetic markers of the risk of tension-type headache and migraine chronization development

Objective: to identify the molecular genetic criteria of the risk of tension-type headache and migraine chronization development.Materials and methods. The detection of the results for the determination of allelic variants was carried out by means of horizontal electrophoresis using a molecular weight marker. The determination of the genotypes of the polymorphic variants of genes was carried out using high resolution melting PCR analysis.Results. Based on the performed molecular genetic studies, it has been established that the statistically significant (p < 0.05) risk factors of tension-type headache chronization are: the identification of the A-allele and AA-genotype of the DBH3 polymorphism of the dopamine-beta-hydroxylase gene DBH, as well as the identification of the G-allele and the GG-genotype of the Intron3SNP polymorphism of the preprotachykinin gene TAC1. It has been found that the statistically significant (p < 0.05) risk factors of migraine chronization are: the identification of the A-allele, GA- and AA-genotypes of the G29A polymorphism of the serotonin transporter gene SLC6A4, as well as the identification of the G-allele and the GG-genotype of the rs7793277 polymorphism of the preprotachykinin gene TAC1.Conclusion. The detection of these polymorphisms of the dopamine and preprotachykinin genes in the blood serum increases the risk of tension headache chronization by 1.395–1.991 times; the risk of migraine chronization by 1.235–1.395 times.

Rat alveolar macrophages express preprotachykinin gene-I mRNA-encoding tachykinins

Although the tachykinins substance P (SP) and neurokinin A have been largely localized to neurons, eosinophils have also been shown to express these peptides. Our aim was to determine whether rat alveolar macrophages (AM) express preprotachykinin gene-I (PPT-I) mRNA that encodes these tachykinins and to examine expression during inflammation. PPT-I mRNA was detected by reverse transcription (RT)-polymerase chain reaction (PCR) in AM and brain (control) but not in peritoneal macrophages. Northern analysis showed that PPT-I mRNA was induced two- to fourfold by in vivo treatment of rats with intratracheal lipopolysaccharide (LPS) and in vitro after 4 h of exposure to LPS. This increase was inhibited by dexamethasone. In situ RT-PCR and immunocytochemistry further confirmed that AM express PPT-I mRNA and SP-like immunoreactivity, respectively, which was enhanced by LPS treatment. A 1.3-kb transcript consistent with PPT-I mRNA was detected by Northern analysis of bronchoalveolar lavage neutrophils. Therefore, rat AM express PPT-I mRNA that is upregulated in AM by LPS and is attenuated by dexamethasone. PPT-I mRNA was also detected in lung neutrophils.