Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), causes 9 million new cases worldwide and 2 million deaths annually. Genetic linkage and association analyses have suggested several chromosomal regions and candidate genes involved in TB susceptibility. This study examines the association of TB disease susceptibility with a selection of biologically relevant genes on regions on chromosomes 7 ( IL6 and CARD11 ) and 20 ( CTSZ and MC3R ) and fine mapping of the chromosome 7p22–p21 region identified through our genome scan. We analyzed 565 individuals from Kampala, Uganda, who were previously included in our genome-wide linkage scan. Association analyses were conducted for 1,417 single-nucleotide polymorphisms (SNP) that passed quality control. None of the candidate gene or fine mapping SNPs was significantly associated with TB susceptibility ( p > 0.10). When we restricted the analysis to HIV-negative individuals, 2 SNPs on chromosome 7 were significantly associated with TB susceptibility ( p < 0.05). Haplotype analyses identified a significant risk haplotype in cathepsin X ( CTSZ ; p = 0.0281, odds ratio = 1.5493, 95% confidence interval [1.039, 2.320]).