Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study
Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study
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DOI：
10.1016/j.humimm.2011.02.016
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发表时间：
2011-05-01
期刊：
影响因子：
2.7
通讯作者：
Stein, Catherine M.
中科院分区：
文献类型：
--
作者：
Baker, Allison R.;Zalwango, Sarah;Stein, Catherine M.
结核病（TB），由结核分枝杆菌（Mtb）引起。每年造成全球900万新病例和200万死亡。遗传连锁和关联分析表明，几个染色体区域和候选基因参与结核病的易感性。本研究检查了TB疾病易感性与7号染色体（IL 6和CARD 1）和20号染色体（CTSZ和MC 3R）区域上的生物学相关基因的选择以及通过我们的基因组扫描鉴定的染色体7 p22-p21区域的精细定位的关联。我们分析了来自乌干达坎帕拉的565名个体，他们之前被包括在我们的全基因组连锁扫描中。对通过质量控制的1，417个单核苷酸多态性（SNP）进行关联分析。候选基因或精细定位SNPs均与结核病易感性无显著相关性（p > 0.10）。当我们将分析限制在HIV阴性个体时，7号染色体上的2个SNP与TB易感性显著相关（p < 0.05）。单倍型分析确定了组织蛋白酶X的显著风险单倍型（CTSZ; p = 0.0281，比值比= 1.5493，95%置信区间[1.039，2.320]）。(C)2011年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
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 CARD] 1) 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]). (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.