Allelic Variants of TNF Superfamily Genes Serve as Markers of Disease Severity in Patients with Chronic Obstructive Pulmonary Disease and Bronchiectatic Disease

Abstract

The distribution of allelic variants of genes of theTNFsuperfamily (TNFA andLTA) was studied in 172 patients with chronic obstructive pulmonary disease (COPD), bronchiectatic disease (n = 22), and in healthy individuals (n = 169). Analysis of the TNFA gene locus –308G → A revealed no differences between the examined groups. Analysis of the LTA gene polymorphic locus +252A → G showed that in patients with COPD, the frequency of the Gallele was significantly higher than that in the control group (χ2 = 3.98, P < 0.05). The presence of this allele in the genotype was correlated with the degree of COPD severity. Thus, in patients with stage II COPD, heterozygous AG genotype predominated (51.3%), whereas in patients with stage III COPD, the frequency of AG genotype was reduced to 32.7% at the expense of increased frequency of GG genotype (14.6%) (χ2 = 6.78, P < 0.05; OR = 4.6, CI 1.37–15.96). The distribution of combined TNFA andLTA genotypes was also studied. In the group of COPD patients, the proportion of individuals with a combination of normal GGTNFA genotype and heterozygous AGLTA genotype was significantly higher (28.5 versus 18.4% in control; χ2 = 4.14, P< 0.05; OR = 1.75, CI = 1.01–3.04). Genotype combinations were characterized at various clinical stages of COPD and bronchiectatic disease (BED). Thus, we have shown for the first time ever that LTA gene alleles and their combinations with the polymorphic variants of the TNFA gene are associated with predisposition to COPD and severity of this disease.