ASSOCIATION OF HLA HAPLOTYPES WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN CONDITIONS OF ORGANIC- SILICON MANUFACTURE

One of the urgent problems of modern medicine is the search for genetic markers of chronic obstructive pulmonary disease (COPD).The aim of the study was to investigate the relationship between HLA haplotypes and COPD in individuals whose illness developed during the professional work in the workshop of organic-silicon production of PJSC "Khimprom" (Novocheboksarsk, Russia).The study included patients with COPD in remission, belonging to the Chuvash ethnic group of Russia - 36 women and 26 men (mean age 45.4±2.3 years). The work experience averaged 15.2±2.4 years, the duration of COPD - 12.3±2.4 years. Smokers made up 22.0±5.8% of the total number of patients. The comparison group was a group of non-patients with COPD workers of organic-silicon manufacture. This group was positioned as "stable" to the development of  COPD. Class I HLA antigens were typed in the standard microlymphocytotoxic test using histotyping anti-HLA sera to 8 HLA-A antigens of the locus A1, A2, A3, A9, A10, A11, A19, A28 and  to 18 HLA-B antigens of  the locus  В5, В7, В8, В12, В13, В14, В15, В16, В17, В18, В21, В22, В27, В35, В40, В41, В42, В53) (CJSC “Interregional Center of Immunogenetics and Histotyping Reagents “Gisans”, St. Petersburg). HLA genotyping of class II alleles was carried out by the multi-primer polymerase chain reaction method in DNA, obtained from nuclear cells of peripheral blood, using reagent sets of the firm “DNA-Technology” (Moscow), according to the reagent manufacturer's method. They were typified by 14 alleles of the DRB1 locus, 8 to the DQA1 alleles and 11 to the DQB1 alleles. The frequencies of two-locus haplotypes were calculated using the computer program "Arlequin v. 3.01 ". The association strength of HLA with COPD was determined by the relative risk (RR) of the formula J. Haldane. The statistical reliability of the difference between RR and 1 was determined by the exact two-sided Fisher test. As a result of the study, the positive association of COPD with haplotypes was established: HLA-A9-DQA1*0501,  A10-DQA1*0103, A28-DQA1*0102,  B7-DQA1* 0103. These haplotypes can be attributed to genetic markers of predisposition to the development of COPD. The negative association with the disease was established for haplotypic combinations of the alleles HLA-A2-B8, A19-DQB1*0502-04, B12-DQB1*0502-04, B27-DQA1*0103, DRB1*01-DQA1*0101, DRB1*07-DQA1*0201, DRB1*13-DQA1 * 0102. This series of haplotypes can be attributed to the category of protective genetic markers of COPD in conditions of organic-silicon manufacture. In continuation of our studies, further research is needed to identify "marker" HLA haplotypes in COPD in other ethnic populations, as well as under the influence of other aggressive air pollutants. The results of the study indicate the association of COPD with a number of specific HLA-haplotypes.

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