The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis

Ioana Streata; January Weiner 3rd; Marco Iannaconne; Gayle McEwen; Marius Sorin Ciontea; Marian Olaru; Rosanna Capparelli; Mihai Ioana; Stefan H E Kaufmann; Anca Dorhoi

doi:10.1371/journal.pone.0163662

The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis

PLoS One. 2016 Sep 29;11(9):e0163662. doi: 10.1371/journal.pone.0163662. eCollection 2016.

Affiliations

¹ University of Medicine and Pharmacy of Craiova, Human Genomics Laboratory, 200638 Craiova, Romania.
² Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
³ University of Naples Federico II, Department of Agriculture, 80055 Naples, Italy.
⁴ "Tudor Vladimirescu" Pneumophtisiology Hospital Runcu, 217390 Gorj, Romania.

Abstract

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.

Grants and funding

This work was supported by intramural funding from Max Planck Society. IS was supported by an EFIS/IL short-term fellowship. MSC, MO, and M. Ioana received funding from the research grant “Vitamin D deficiency and immunogenetic factors in relation to Tuberculosis (RID-TB)” through UEFISCDI—Young Research Teams, PN-II-RU-TE, 217EU/2013 and 163/01/10/2015. This work was also supported by the EU Seventh Framework Programme (FP7/2007-2013) through grant 305279. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.