Association of toll-like receptor 2 polymorphisms with susceptibility to pulmonary tuberculosis in Sudanese

Abstract

Background: Mycobacterium tuberculosis (MT) is a leading cause of death worldwide, and the incidence of the tuberculosis) has been escalating due to the convergence of multidrug-resistant strains and HIV infection epidemics. Genetic and nongenetic factors of both the bacterium and the host have impact on the host response to MT. Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. It has been proved that viable Mycobacterium bacilli contain distinct ligands that activate cells via TLR2. Aim: This study was conducted to test the association of TLR2 gene polymorphisms with susceptibility to pulmonary tuberculosis in Sudanese. Subjects and methods: A case-control study of 207 Sudanese patients with pulmonary tuberculosis and 395 healthy controls was used. Three tag single nucleotide polymorphisms (SNPs) in TLR2 gene and its 3-Kb flanking regions on chromosome 4 were selected. The tag approach was set to r2 > 0.8 and minor allele frequency (MAF) > 0.2. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism method. Results: Genotypes of the 3 SNPs (rs1816702, rs3804099, and rs7656411) were estimated and compared. The stepwise regression procedure demonstrated that elimination of rs1816702 and rs3804099 from the model did not have any significant effect (p =.0685,.7300 respectively), while rs7656411 was significantly associated with tuberculosis susceptibility (p =.0372). TLR2 rs7656411 TG and GG genotypes frequencies were higher in pulmonary tuberculosis patients (OR = 1.74, 95% CI = 1.09–2.78, and OR = 2.24, 95% CI = 1.37–3.68 respectively). The haplotype TCG of TLR2 SNPs was also associated with TB susceptibility (p =.0004). Conclusion: Our study suggests that allele G of rs765641 on TLR2 gene might influence susceptibility to pulmonary tuberculosis in Sudanese.