Mast cells are a major producer of histamine, which binds to H1R, H2R, H3R, and H4R. H1R and H4R play important roles in allergic diseases, such as urticaria and asthma; H2R stimulates gastric acid secretion; and H3R plays a crucial role in the control of sleep–wake behavior (49). This evidence concerns the gene HRH2 and urticaria.