Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
BMC Med Genet. 2010 Jan 30;11:17. doi: 10.1186/1471-2350-11-17.
To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.
A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.
We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/microl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/microl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/microl, p = 0.004).
TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.
为了研究 Toll 样受体 2 多态性是否会影响肺结核的易感性、其表型和血液淋巴细胞亚群。
共检测了 368 例研究对象，包括 184 例肺结核患者和 184 例健康对照者，对 TLR2 基因座 -100（微卫星鸟嘌呤-胸腺嘧啶重复序列）、-16934（T>A）、-15607（A>G）、-196 到-174（插入缺失）和 1350（T>C）的多态性进行了检测。还对 86 例肺结核患者进行了外周血淋巴细胞亚群的检测。
我们新发现一个与肺结核易感性相关的单倍型[A-G-(插入)-T]（p = 0.006，假发现率 q = 0.072）。有全身症状的肺结核患者 -196 到-174 缺失/缺失基因型频率低于无全身症状的患者（5.7%比 17.7%；p = 0.01）。携带缺失/缺失基因型的肺结核患者血液 NK 细胞计数高于携带插入等位基因的患者（526 比 243.5 细胞/微升，p = 0.009）。有胸膜炎的肺结核患者 1350CC 基因型频率高于无胸膜炎的患者（12.5%比 2.1%；p = 0.004）。携带 1350CC 基因型的肺结核患者血液 NK 细胞计数高于携带 T 等位基因的患者（641 比 250 细胞/微升，p = 0.004）。携带 GT 重复短等位基因纯合子的肺结核患者血液 NK 细胞计数高于携带一个或没有短等位基因的患者（641 比 250 细胞/微升，p = 0.004）。
TLR2 遗传多态性影响肺结核的易感性。TLR2 变体在肺结核表型的发展中起作用，可能通过控制 NK 细胞的扩增来起作用。
