title: 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]).
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Baker
authors.forename: Sarah
authors.initials: S
authors.lastname: Zalwango
authors.forename: LaShaunda L
authors.initials: LL
authors.lastname: Malone
authors.forename: Robert P
authors.initials: RP
authors.lastname: Igo
authors.forename: Feiyou
authors.initials: F
authors.lastname: Qiu
authors.forename: Mary
authors.initials: M
authors.lastname: Nsereko
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Pamela
authors.initials: P
authors.lastname: Supelak
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D056663:Cathepsin Z / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D014454:Uganda
chemical_list: D053468:CARD Signaling Adaptor Proteins; D015850:Interleukin-6; C505392:MC3R protein, human; D044104:Receptor, Melanocortin, Type 3; D056663:Cathepsin Z; C426242:CARD11 protein, human; D006162:Guanylate Cyclase