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Interferon- and Interleukin-10 Gene Polymorphisms in Pulmonary Tuberculosis

Department of Internal Medicine, Microbiology, and Clinical Biochemistry, Hospital La Paz; and Department of Pharmacology and Therapeutics, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

Correspondence and requests for reprints should be addressed to Francisco Arnalich, Internal Medicine Service, Hospital La Paz, Maternidad Planta 8, Paseo de la Castellana 241, 28046 Madrid, Spain. E-mail: francisco.arnalich{at}uam.es

Several genes coding for different cytokines may affect host susceptibility to tuberculosis. This study investigates the relationship of the single base change polymorphic variants identified in the first intron of interferon- (+874 T/A) and in the promoter region of interleukin-10 gene (-1,082 G/A), with cytokine production by peripheral blood mononuclear cells and tuberculosis susceptibility. We studied a Spanish population of 113 patients with culture-proven pulmonary tuberculosis, 207 healthy close contacts (125 tuberculin reactive and 82 tuberculin negative), and 100 healthy tuberculin-negative control subjects. Multiple logistic regression analysis showed that individuals homozygous for the interferon- (+874) A allele had a 3.75-fold increased risk of developing tuberculosis (95% confidence interval, 2.26–6.23, p = 0.0017). Stimulated production of interferon- by peripheral mononuclear cells from patients with genotype AA was depressed compared with that of non-AA homozygotes at the time of diagnosis and after completion of therapy. Multivariate analysis showed that the presence of an AA genotype and the absolute number of lymphocytes were the only independent predictors of interferon- production. In contrast, the different rates of interleukin-10 production associated with the interleukin-10 polymorphism did not affect susceptibility to tuberculosis. Thus, a genetic defect in the production of interferon- in individuals homozygous for the (+874) A allele could contribute to their increased risk of developing tuberculosis.

Key Words: gene polymorphisms • tuberculosis susceptibility • cytokine production • interferon- • interleukin-10

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