Common polymorphisms in TLR4 gene associated with susceptibility to pulmonary tuberculosis in the sudanese

Abstract

SETTING: Host genetic risk factors influence susceptibility to tuberculosis (TB). There is ample evidence supporting the involvement of toll-like receptor 4 (TLR4) in mycobacterial infection. OBJECTIVE: To study the relationship between the TLR4 gene and TB susceptibility in the Sudanese population. DESIGN: A case-control study was conducted among 207 patients with pulmonary TB and 395 healthy controls. Ten tag single nucleotide polymorphisms (SNPs) of the TLR4 gene were genotyped using restriction digestion or hybridisation assays, and analysed. RESULTS: The genotypes were in Hardy-Weinberg equilibrium. After controlling for sex using the Mantel-Haenszel test, four SNPs showed significant differences between cases and controls, even after correction of multiple comparisons by Bonferroni procedure. The Mantel-Haenszel estimates of allelic odds ratios for the high-risk alleles were 1.67 for rs1927911 (P = 0.0001), 1.85 for rs5030725 (P = 0.0008), 2.14 for rs7869402 (P = 1.87e-07) and 2.31 for rs1927906 (P = 1.23e-10). Haplotype analysis showed that rs1927911 and rs5030725 were in one haplotype block, and rs7869402 and rs1927906 were in another haplotype block. Conditional haplotype analysis suggested the presence of one causal variant downstream of a recombination hot spot at the 3′ region of the TLR4 gene. CONCLUSION: This is the first study to show that common TLR4 polymorphisms are associated with TB susceptibility in the Sudanese population.