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    • Some SNPs have been identified

    2021-09-29

    Some SNPs have been identified for HRH in cancer (Table 4). Looking into breast cancer research, H4 receptor polymorphisms have been recently associated with the malignancy of the disease. This was evidenced upon the analysis of genotypes and haplotypes of a Chinese Han population; this study showed that SNPs rs623590, rs11662595, and rs1421125 had a significant association with the risk and malignancy of breast cancer (He et al., 2013). Further investigations need to be undertaken in order to demonstrate if these results are replicable in other populations and understand if this linkage is ethnicity-based or not. Studies related to gastric carcinoma and H4 receptors have also been carried out, where no significant difference was found between copy number variations on H4 receptor BMS-650032 mg and patients with gastric carcinoma, but there was a substantial correlation between copy number deletions and H4 receptor down regulation. This suggests that abnormalities in H4 receptor have a potential role in histamine-mediated regulation of tumour growth in gastric cancer (Zhang et al., 2012). Analysis carried out on the H2 receptor in gastric carcinoma identified promoter polymorphism rs2607474 to be associated with the disease, especially the GG homozygous genotype. This polymorphism was identified by the same group to be associated with gastric mucosal atrophy as previously mentioned. And this association with gastric cancer was even higher at an advanced age where the atrophy and metaplasia scores were found to be higher (Arisawa et al., 2012). Due to the location of this SNP in an important region for gene regulation, it seems like it has an important implication in gene transcription, but further analysis are needed to prove this biological significance. With the completion of the Human Genome Project in April 2003, numerous studies have emerged which help to understand the genetic basis of many common phenotypes of biochemical importance. Several diseases have been studied and are now known to be caused by a combination of multiple genetic and environmental factors. Deeper understanding of these factors can prove to be a useful tool in leading to better markers and targets to treat human diseases (Consortium, 2003, Gabriel et al., 2002). The knowledge to date on histamine receptor polymorphisms generates even more interest in identifying novel genetic variations that contribute to a disease, especially with the importance histamine has in biological processes.
    Acknowledgements The Strategic Educational Pathways Scholarship (Malta) funded the parts of the research work disclosed in this publication. The scholarship (SM) is part-financed by the European Union — European Social Fund (ESF) under Operational Programme II — Cohesion Policy 2007–2013, “Empowering People for More Jobs and a Better Quality of Life. Further support has been given by the EU COST Action BM0806 and to HS by the COST Actions BM1007, CM1103, and CM1207 as well as the Hesse LOEWE Schwerpunkte Fh-TMP, OSF and NEFF, the Else KrönerStiftung TRIP and the Deutsches Konsortium für Translationale Krebsforschung, DKTK.
    Introduction The H4 receptor is predominantly expressed on inflammatory cells and lymphoid tissues (for review, see Leurs et al., 2009, Marson, 2011) although its occurrence in the brain has been suggested as well. H4 receptor mRNA was found in the brain by some but not all investigators (reviewed by Marson, 2011, Schneider et al., 2015). Studies dedicated to the identification of H4 receptors on the protein level must be assessed critically since in those studies (e.g., Connelly et al., 2009, Lethbridge and Chazot, 2010) H4 receptor antibodies were used that did not fulfill the stringent criteria for antibodies against G protein-coupled receptors (Michel et al., 2009, Seifert et al., 2013). There is also evidence from functional studies that H4 receptors may play a role in the CNS, including electrophysiological (Desmadryl et al., 2012, Connelly et al., 2009) and behavioural investigations (Ballerini et al., 2013, Saligrama et al., 2012, Galeotti et al., 2013). A critical appraisal of those studies is given in the review by Schneider and Seifert (2016), appearing in this issue of Neuropharmacology.