Genetic susceptibility to different clinical forms of tuberculosis in the Peruvian population

Racial variation, twin studies, segregation analyses, linkage and association studies all suggest that genetic factors play an important role in predisposition to tuberculosis. Many previous studies have been performed with pulmonary TB patients, as the most prevalent form of clinical TB (nearly 95%), and very few of them have considered extrapulmonary TB. The present study evaluates the effects of variation in eight candidate genes (LTA, TNF, IL1B, IL1RN, IL10, TGFB1, TIRAP and P2X7) with pulmonary, pleural, miliary and other extrapulmonary forms of TB in a Peruvian population from the North of Lima. 626 TB cases and 513 healthy controls were enrolled in this study. LTA(+368) and IL10(-592) were associated with different clinical forms of TB (P<0.05). LTA(+368) genotype A/A was protective for pleural TB, LTA(+368) G/A was correlated with susceptibility to miliary TB. Genotypes A/A and G/A were associated with protection and susceptibility respectively when considering all extrapulmonary TB forms versus either healthy controls or pulmonary TB patients. Carriers of IL10(-592)*C were under-represented among those with pulmonary TB and all TB forms (P<0.001). IL10(-1082)-IL10(-592) haplotypes showed different distributions among patients with pulmonary TB and all TB forms (P<0.01) when compared to healthy controls. In addition, IL10(-1082)-IL10(-592) haplotypes showed differences between pleural, miliary and all forms of extrapulmonary TB when compared with pulmonary TB (P<0.05). All findings are consistent with an under-representation of the IL10(-1082)*A-IL10(-592)*A haplotype in pulmonary TB patients. These results suggest that the polymorphisms LTA(+368) and IL10(-592), or variants in strong linkage disequilibrium, variably affect susceptibility to the differing clinical forms of TB in Peruvians.