ADRB2, ADAM33 and AAT gene polymorphisms and IgE-mediated asthma in Russian patients

Background: Asthma is complex disease which pathogenesis is a mix of environmental and genetic factors. A predisposition of airways to bronchoconstriction is one of main risk factors of asthma. Therefore genes which are directly or indirectly involved in bronchoconstriction are of great interest in asthma genetics. The aim of our study was to evaluate an effect of polymorphisms Arg16Gly and Glu27Gln in beta-2-adrenergic receptor ( ADRB2 ) gene, Glu264Val and Glu342Lys in alpha1-antitrypsin ( AAT ) gene and ST+4 in a disintegrin and metalloprotease domain 33 ( ADAM33 ) gene in predisposition to IgE-mediated asthma in Russian patients from Moscow. Methods: 230 patients with IgE-mediated asthma and 214 healthy individuals were examined. The genotyping was performed by MALDI-TOF mass spectrometry. Results: Allele G of Arg16Gly and allele C of Glu27Gln (both markers in ADRB2 gene) showed strong association with atopic bronchial asthma ( OR = 2.51 and 1.46, respectively, p < 0.05). Allele A of Arg16Gly and allele G of Glu27Gln of that gene was found to have protective effect ( OR = 0.76 and 0.69, respectively, p < 0.05). Additionally one of haplotypes of ADRB2 gene (A-G) also was associated with protection from asthma development ( OR = 0.43, p = 0.008). No association was detected between other studied SNPs and development of asthma. Conclusion: Our results suggest that Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene strongly contribute to predisposition to IgE-mediated asthma. Probably ADAM33 and AAT genes are not directly involved in predisposition to asthma and those genes possibly realize their effects when asthma is already developed.