الفهرس 
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Abstract
Tuberculosis (TB) is a top infectious world killer disease with an estimated 10 million individuals fall ill with TB bacteria every year. The highest worldwide disease prevalence is reported in low- and middle-income countries which are found in Bangladesh, China, India, Indonesia, Nigeria, Pakistan, Philippines and South Africa. Only 5 – 15 % fall ill with active TB, The rest have TB infection but are not diseased and don’t transmit the infection. Every year 1.5 million individual die from TB. TB leads to death of people with HIV and contributor to antimicrobial resistance.
Toll-like receptors (TLRs) are “pattern recognition receptors” (PRRs) expressed on macrophages and leukocytes. TLRs are critical to innate immune responses and tuberculosis adapts TLR function to evade immune clearance.
In this cross sectional study, convenience sample of 238 unrelated individuals were obtained. They were divided into 140 patient subjects with diagnosis of pulmonary tuberculosis and 98 household healthy subjects as controls. All subjects were genotyped for TLR9.rs5743836 and TLR2.rs5743708 SNPs by PCR-RFLP analysis while TLR9.rs352139 SNPs by ARMS-PCR (amplification refractory mutation system-PCR).
The data revealed that the “GG” genotype and “G” allele in TLR2 Arg753Gln are the most frequent genotype/allele in both groups; while the “AA” genotype and “A” allele are the least frequent ones. A total loss of “AA” genotype occurred in the control group. The present study did not find any significant association between TLR2 Arg753Gln polymorphism and the risk of tuberculosis.
The data, show also that the TLR9.rs5743836 (-1237T/C) a statistically significant increase in “TC” genotype (p = 0.012) and “T” allele (p = 0.003) in TB patients compared with the controls. On the other hand, “TT” genotype and “C” allele were elevated significantly in the control group (p = 0.02 and p = 0.001, respectively). Accordingly, “TC” genotype (OR=3.282, CI: 1.193-9.033) and “T” (OR = 2.253; CI: 1.301-3.921) allele might be considered as a risk factors for TB infection, while “TT” genotype (OR = 0.247; CI: 0.091-0.671) and “C” allele (OR = 0.416; CI: 0.239-0.724) might be considered as a protective one. In addition, the data show that the TLR9.rs352139 (1174G/A had insignificant genotypic/allelic distributions. Genotype “GA” and “G” allele were the most frequent genotype/allele in Egyptian patients with pulmonary tuberculosis. “AA” genotype is the least frequent and might be considered a risk factor of tuberculosis (OR = 2.252; CI: 0.514-12.429).
Finally, eight haplotypes are constructed the three Single Nucleotide Polymorphisms (SNPs), which showed that “GTG” and “GTA” haplotypes were the highest frequency in both groups; while “ATG” was the least frequent haplotype. The “ACA” and “ACG” haplotypes are totally disappeared. Interestingly, “GCG” haplotype and “ATG” showed a significant decrease in TB patients (p = 0.004 and p = 0.001, respectively).The genotype frequencies of TLR2 at Arg753Gln and TLR9 at -1237T/C in all subjects showed the same genetic variation, indicating that TLR2 Arg753Gln and TLR9 (-1237T/C) appeared to be in LD in the Egyptian population (D’ = 0.9856, r2= -0.0675). On the other hand, the LD pattern between TLR9 -1237T/C and TLR9 +1174G/A showed no LD, with a D’ value of 0.082 and r2 value of -0.0273.
In conclusion, there was no association between the polymorphisms in TLR2 and TLR9 and TB risk overall, but TLR9 -1237 T/C (5743708) might be associated with increased TB risk in Egyptians. Whether the observed association was due to causal effect requires additional larger-scale epidemiological studies to validate our results.