Genetic risk score constituted by Toll-like receptor and matrix metalloproteinase single nucleotide polymorphisms helps predict tuberculosis status progression

<b>Purpose:</b> TB remains an important global infectious disease, which was considered a disease of continual process. We aim to find out the risk scores composed of genetic factors to predict the clinical progression of TB status. <b>Methods:</b> We recruited study participants and collected their samples prospectively. 29 SNPs from <i>TLR1</i>, <i>TLR2</i>, <i>MRC1</i>, <i>MMP1</i>, <i>MMP8</i>, <i>MMP9</i> and <i>TIMP2</i> gene were analyzed with the adjustment of covariates. <b>Results:</b> 57 uninfected contacts, 203 LTBI contacts and 400 active TB patients were recruited. In analyzing the association between SNPs and TB status (active TB vs LTBI), <i>TLR1</i> rs5743580 genotype was associated with higher risk of active TB (genotypic, AA, OR:2.13, 95% CI:1.11-4.11). <i>TLR1</i> rs5743551 genotype was also associated with lower risk of active TB (dominent, AA, OR:0.621, 95% CI:0.239-0.968). <i>TLR2</i> rs3804100 genotype was associated with higher risk for active TB (genotypic, TC vs TT, OR:1.85, 95% CI:1.18-2.90; dominant, CC, OR:1.84, 95% CI:1.19-2.83; additive, OR:1.58, 95% CI:1.11-2.25). <i>MMP8</i> rs2508383 genotype was associated with lower risk of active TB (genotypic, CT vs CC, OR:0.62, 95% CI:0.40-0.96; dominant, TT, OR:0.63, 95% CI:0.42-0.96). A polygenic risk score was created with <i>TLR1</i> rs5743580, <i>TLR2</i> rs3804100 and <i>MMP8</i> rs2508383 SNPs, which was associated with higher risk of progression to active TB (OR:2.52, 95% CI:1.49-4.24) in multivariate logistic regression model. <b>Conclusions:</b> Several immune and tissue destruction enzyme SNPs were associated with TB status. We created a genetic risk score using <i>TLR1</i>, <i>TLR2</i>, <i>MMP8</i> SNPs, which could help stratify the risk of active TB infection in Taiwanese population.