Streata Ioana, Weiner January, Iannaconne Marco, McEwen Gayle, Ciontea Marius Sorin, Olaru Marian, Capparelli Rosanna, Ioana Mihai, Kaufmann Stefan H E, Dorhoi Anca
University of Medicine and Pharmacy of Craiova, Human Genomics Laboratory, 200638 Craiova, Romania.
Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
PLoS One. 2016 Sep 29;11(9):e0163662. doi: 10.1371/journal.pone.0163662. eCollection 2016.
Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here.
CARD9基因中的遗传变异易导致炎症性疾病和慢性感染性疾病。肺结核（TB）是一种影响肺部的慢性感染性疾病，在CARD9基因缺陷的小鼠中是致命的。我们推测CARD9基因的多态性会影响人类肺结核的进展以及与疾病相关的肺损伤。我们在一个白种人队列中测试了肺结核患者和健康受试者中CARD9多态性位点rs4077515、rs10781499和rs10870077的基因型分布。这些单核苷酸多态性（SNP）处于连锁不平衡状态，且在肺结核组中没有任何单倍型显著富集。我们测定了白细胞总数和分类计数、红细胞沉降率以及细胞因子和趋化因子的血浆丰度，作为全身炎症的标志物，并对胸部X光片进行评分以评估肺结核患者的肺部受累情况。大多数疾病参数与CARD9单倍型独立分离。与多因素慢性炎症不同，CARD9基因中选定的遗传变异显然不会影响肺结核患者的宿主反应，至少在本文分析的人群中是这样。
