Common Polymorphisms in the TLR4 Gene are Associated with Susceptibility to Pulmonary Tuberculosis in Sudanese

SETTING: Host genetic risk factors influence the 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 Sudanese. DESIGN: A case-control study was conducted by recruiting 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 hybridization assays, and analyzed. RESULTS: The genotypes were in Hardy-Weinberg equilibrium. With Mantel-Haenszel tests controlled for gender, 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 suggests the presence of one causal variant downstream of a recombination hotspot 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 a Sudanese population.