Association of IL12RB1 polymorphisms with pulmonary tuberculosis in adults in Morocco

The Journal of Infectious Diseases
Natascha RemusLaurent Abel

Abstract

Five disease-causing genes, including the IL12RB1 gene that encodes the beta 1 chain of the receptor for interleukin (IL)-12 (IL-12R beta 1), are known to be associated with the syndrome of Mendelian susceptibility to mycobacterial diseases. Some IL-12R beta 1-deficient patients present with tuberculosis as the only clinical phenotype. A comprehensive genetic study of IL12RB1 was conducted among 101 Moroccan families, including 157 offspring (age, >15 years) who had culture-positive pulmonary tuberculosis (PTB). The promoter, exons, and flanking intron regions of IL12RB1 in 40 randomly selected patients with PTB were entirely sequenced, leading to the detection of 19 variants (including 10 novel mutations). Blood cells obtained from individuals who were homozygous for any of the 13 most common variants responded to IL-12, indicating that these polymorphisms were not loss-of-function mutations. By use of a family-based study, 2 promoter polymorphisms that were in strong linkage disequilibrium were found to be associated with PTB, especially -2C-->T (odds ratio for CT or TT vs. CC, 2.69 [95% confidence interval, 1.19-6.09]). This result suggests that IL12RB1 polymorphisms might influence the risk of development of PTB in adults.

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