Association analysis of polymorphic variants in ALDH7A1, AOC1, PSAP, ADCYAP1 genes involved in the histamine metabolism with asthma development in individuals from the republic of Bashkortostan

Many environmental and genetic factors are involved in asthma development, among which an important role in the disease formation and response to antihistamine therapy belongs to genes involved in the histamine metabolism (HRH1, HRH2, HRH3, HRH4, HDC, HNMT, AOC1, MAOB, ALDH7A1, etc.). Histamine is a central mediator of allergic inflammation the release of which leads to contraction of the bronchial smooth muscles, bronchial secretion and edema of the respiratory mucosa. The use of antihistamines performing competitive blockade of histamine receptors leads to inhibition of histamine effects. The aim of this study was to assess the role of polymorphic variants of aldehyde dehydrogenase 7 family member A1 ALDH7A1 (rs13182402), amine oxidase copper containing 1 AOC1 (rs1049793), prosaposine PSAP (rs11000016), adenylate cyclase activating polypeptide 1 ADCYAP1 (rs2231187) genes involved in the histamine metabolism in asthma development in individuals from the Republic of Bashkortostan. DNA samples of 846 unrelated individuals of different ethnicity living in the Republic of Bashkortostan were used as the study material. Genotyping of polymorphic variants was performed by real-time PCR and RFLP analysis. The statistically significant association of the rs2231187*AA genotype and the rs2231187*A allele of the ADCYAP1 gene with asthma, the rs2231187*A allele of the ADCYAP1 gene with disease manifestation in childhood, the rs2231187*AA genotype of the ADCYAP1 gene and the rs13182402*G allele of the ALDH7A1 gene with severe and moderate asthma was established in Bashkirs. The rs1049793*CC genotype and the rs1049793*C allele of the AOC1 gene were associated with asthma in Russians. The results of this study are complementary to the previously published data regarding genetic aspects of asthma pathogenesis that suggest the involvement of ALDH7A1, ADCYAP1 and AOC1 gene polymorphisms in asthma development.

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