Association analysis of C242T and A640G polymorphisms in the gene for p22phox subunit of NADPH oxidase with the risk of bronchial asthma: A pilot study

摘要

Genetic control of free radical oxidation, generation of reactive oxygen species, as well as of preoxidant and antioxidant balance in airway diseases, including bronchial asthma, is an important issue of the research in pulmonology. The present study is the first investigation of association between two common polymorphisms, C242T (exon 4) and A640G (3′ untranslated region), within the NADPH oxidase gene (CYBA) and the risk of bronchial asthma. Samples of asthma patients (n = 209) and healthy controls (n = 210) of Russian nationality were examined. Genotyping of the CYBA C242T and A640G polymorphisms was performed using polymerase chain reaction and restriction fragment length polymorphism. It was demonstrated that the frequency of heterozygous CYBA genotype A640G in bronchial asthma patient group was lower than that in control group (OR = 0.66; 95%CI, 0.45–0.97; P = 0.04). Separate analysis of different clinical pathogenetic variants of the disease showed that homozygous wild-type CYBA genotype 640AA was associated with the increased risk of allergic bronchial asthma (OR = 1.76; 95%CI, 1.07–2.90; P = 0.03), while heterozygous CYBA genotype A640G was associated with the decreased risk of this form of the disease (OR = 0.63; 95%CI, 0.41–0.96; P = 0.03). Thus, a new candidate gene for allergic bronchial asthma was discovered. Possible mechanisms of the involvement of CYBA in the development of asthmatic phenotype are discussed.