Association of Polymorphic Variants of Key Histamine Metabolism Genes and Histamine Receptor Genes with Multifactorial Diseases

Abstract

Histamine is a biologically active substance of local effect, but is involved in the regulation of different processes in the body, including the pathogenesis of diseases. In the present review, molecular genetic, clinical, and experimental studies on the role of histamine and key genes of its metabolism in the pathogenesis of diseases are summarized. Data on associated polymorphic variants (30 SNPs, 1 CNV) of key histamine metabolism genes with multifactorial diseases are given, including HDC (involved in the synthesis of histamine), HNMT, AOC1, MAOB, ALDH7A1 (involved in the processes of histamine degradation), and HRH1, HRH2, HRH3, HRH4 (histamine receptors): associations were established with allergic and oncological diseases, diseases of nervous and cardiovascular systems, gastrointestinal tract, metabolic disorders, etc. A nonrandomness of established associations of histamine metabolic pathway genes with pathological conditions is supported by clinical observations and experimental studies performed on model objects and cell lines. Moreover, according to clinical and experimental data, a wider range of pathological conditions in which risk structural and functional peculiarities of key histamine metabolic pathway genes will make a certain contribution can be expected. The questions of the complexity of determining the significance of histamine level and structural and functional peculiarities of histamine metabolic pathway genes in terms of a positive/negative effect on the body, as well as some possible reasons for inconsistency of association studies performed in different ethnoterritorial groups, are discussed.