Aim. The aim of this study was to examine the association of cytokine gene polymorphism in the Macedonian population with Tuberculosis (TBC), as a part of the International Project Cytokine Polymorphism Component (CPC), 13th IHWC.

Methods. The Macedonian population consists of: 125 healthy unrelated individuals and 75 patients with culture- or biopsy-proven tuberculosis. The definition of clinical phenotype was based on the International Classification of Disease 9 classification. Blood samples were collected after written consent, DNA was isolated from peripheral blood leukocytes by the phenol-chlorophorm extraction method and samples were stored in the Macedonian Human DNA Bank (hDNAMKD). Thirteen  cytokine genes were identified as candidates for the CPC: gamma-interferon (IFNg); interleukin (IL) 1 alpha (IL-1a); IL-1 beta (IL-1b); IL-1 receptor (IL-1R); IL-1R antagonist (IL-1RA); IL-2; IL-4; IL-4 receptor alpha (IL-4Ra); IL-6; IL-10; IL-12B; TGF beta 1 (TGF-b1); and TNF alpha (TNF-a). Cytokine genotyping was performed by PCR-SSP method (Heidelberg kit). Agarose gel electrophoresis on a 2% agarose gel revealed a positive or a negative specific amplification for each well. Subsequently, the results were entered in the Cytokine-SCORE software and analysed automatically. The population genetics analysis package was used for analysis of the cytokine data for this report. Comparisons of different genotypes for two groups were tested by the the c² test. Crude odds ratios (OR), as estimates of the relative risk, were calculated with 95% CI.

Results. It was found significant association between the Macedonian patients with TBC and: 1) cytokine alleles (IL-1R pstl 1970, and TNFa-238) and 2) cytokine genotypes (IL-1b+3962/C:T, IL-1R pstl 1970/T:T, IL-1RA mspa11100/C:C, IL-1RA mspa11100/T:T, TGFb1cdn25/C:G, TNFa-238/A:G, IFNg UTR5644/A:A and IFNg UTR5644/A:T).

Conclusion. It is concluded that cytokine gene polymorphism in the Macedonian population is associated with Tuberculosis.