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: Allison R Baker, Sarah Zalwango, LaShaunda L Malone, Robert P Igo Jr, Feiyou Qiu, Mary Nsereko, Mark D Adams, Pamela Supelak, Harriet Mayanja-Kizza, W Henry Boom, Catherine M Stein
• Journal: Human immunology (Hum Immunol) Vol. 72 Issue 5 Pg. 426-30 (May 2011) ISSN: 1879-1166 [Electronic] United States
• PMID: 21354459 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• CARD Signaling Adaptor Proteins
• Interleukin-6
• MC3R protein, human
• Receptor, Melanocortin, Type 3
• Cathepsin Z
• CARD11 protein, human
• Guanylate Cyclase

Topics

• Adolescent
• Adult
• Aged
• CARD Signaling Adaptor Proteins (genetics, metabolism)
• Cathepsin Z (genetics, metabolism)
• Child
• Child, Preschool
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Guanylate Cyclase (genetics, metabolism)
• Haplotypes
• Humans
• Infant
• Interleukin-6 (genetics, metabolism)
• Male
• Middle Aged
• Mycobacterium tuberculosis (pathogenicity, physiology)
• Polymorphism, Single Nucleotide
• Receptor, Melanocortin, Type 3 (genetics, metabolism)
• Tuberculosis, Pulmonary (genetics, immunology, physiopathology)
• Uganda