Analysis of the N-Acetyltransferase 2 Gene Polymorphism in the Patients with Chronic Obstructive Pulmonary Disease and in Populations of the Volga–Ural Region

Restriction fragment-length polymorphism of the gene coding for N-acetyltransferase 2 (NAT2) was typed in populations of the Volga–Ural region (Bashkirs, Tatars, Chuvashes, Udmurts, and Russians) as well as in patients with chronic obstructive pulmonary disease (COPD) and in healthy individuals. Rapid and slow acetylator phenotypes were determined based on the presence or absence of the KpnI, TaqI, and BamHI restriction endonuclease recognition sites. The proportion of slow acetylators in the populations examined varied from 40.00% in Bashkirs to 64.15% in Chuvashes with statistically significant difference between these two ethnic groups (² = 5.7; P = 0.02). Overall, in the Volga–Ural populations slow acetylators represented 56.25% of the subjects examined. This value was similar to those presented in other studies of Caucasoid populations. In the COPD patients a statistically significant decrease of the slow acetylator frequency to 48.28% compared to healthy individuals (62.18%) was observed (² = 4.60; P = 0.036). The data obtained suggest a possible association between the drug resistance in the COPD patients with the rapid acetylator phenotype, which can lead to the development of the chronic form of the disease.     

Polymorphism of Xenobiotic Metabolism Genes in Petrochemical Workers

Genetic polymorphism of xenobiotic metabolizing enzymes responsible for individual susceptibility to different environmental factors was examined in a cohort of petrochemical workers occupationally exposed to adverse action of chemical compounds. Molecular genetic analysis of the I462V mutation in exon 7 of the CYP1A1gene demonstrated close similarity between the genotype and allele frequency distribution patterns in the industrial and control groups. No association between the CYP1A1polymorphic alleles and genotypes and the duration of service and concomitant diseases was observed. The odds ratio of the disease development in the workers carrying heterozygous CYP1A1 mutant allele was 2.2. Analysis of the GSTM1 gene polymorphism demonstrated a decrease in the frequency of the homozygous deletion carriers in the workers compared to the control group. There were no substantial differences between the industrial and control groups with respect to the frequencies of rapid and slow acetylator genotypes revealed at the analysis of the NAT2 gene polymorphism. However, considering the concomitant diseases, in the corresponding industrial subgroup a clear trend towards lower frequency of rapid acetylators was demonstrated. In addition, the odds ratio of the disease development for the workers with slow acetylator phenotype was 1.7.