Importance of common TLR2 genetic variants on clinical phenotypes and risk in tuberculosis disease in a Western Chinese population.

Objectives: Abundant studies have suggested that TLR2 genetic variants involve in susceptibility to TB infection. We tried to verified the hypothesis that TLR2 genetic loci effect on the susceptibility to TB in the Western Chinese population.

Methods: A total 1109 individuals (634 TB patients and 475 healthy controls) were genotyped for rs3804099, rs3804100 and rs76112010 by using a custom-by-design 2x48-Plex SNP scan TM Kit. The statistical analysis between candidate 3 SNPs and risk and phenotypes of TB were conducted in this study. Significant SNPs were further interrogated in relation to TB susceptibility to TB infection and clinical phenotypes.

Results: None of the three genetic loci (rs3804099, rs3804100 and rs76112010) showed statistically significant differences between all TB cases and healthy controls in genotype, allele frequencies and genetic models (all p > 0.05). Statistical comparisons of retreatment TB cases and healthy controls or primary cases revealed that rs3804099 was significantly associated with the increased risk of developing TB in Western Chinese population. For genotypes frequencies, the subgroups of retreatment TB group versus healthy control group analysis and retreatment TB group versus primary TB group analysis results showed the p = 0.041 and p = 0.002 respectively. For recessive model, the subgroup of retreatment TB group versus healthy control group and retreatment TB group versus primary TB group analyses showed the p = 0.028 and P = 0.002 after Bonferroni correction respectively. Furthermore, analysis of the genotypes of rs76112010 in relation to clinical phenotypes of active TB using the dominant model demonstrated that it was strongly correlated with different hematological parameters (Erythrocyte P = 0.043, Hemoglobin P = 0.047, Hematocrit P = 0.027).

Conclusion: Our study presented the significant associations of rs3804099 with TB susceptibility in the retreatment TB subgroup analysis. Our study proposed that common TLR2 genetic variants may influence TB development and disease phenotypes in Western Chinese population.