ABSTRACT
Only 5-10% of people infected with Mycobacterium tuberculosis develop active tuberculosis which suggests a role of genetic variation in host immunity. Genetic variants in TLRs are potential indicator for host susceptibility and outcome of several diseases. We explored the association of nonsynonymous genetic variants (Met1Val) with Toll-like receptor 8 in Pakistani population. Genotypic and allelic distribution of TLR8 polymorphism (rs3764880) in patients with TB and healthy donors from different areas of southern Punjab, Pakistan, was determined. Results provide that our population is highly influenced by TLR8 Met1Val SNP for TB, and G allele appeared to increase TB susceptibility. Mutant genotype GG or G/- and G allele was significantly higher among all the categories of cases than in controls. Among different levels of bacillary load and genotypes, GG or G/- and G allele significantly supports the incidence of 2 + class for bacterial load.
Subject(s)
Mycobacterium tuberculosis/immunology , Toll-Like Receptor 8/genetics , Toll-Like Receptor 8/immunology , Tuberculosis, Pulmonary/immunology , Adolescent , Adult , Alleles , Bacterial Load/genetics , Child , Child, Preschool , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Pakistan , Polymorphism, Single Nucleotide/genetics , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/microbiology , Young AdultABSTRACT
Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide. Pakistan ranks sixth on the list of 22 high-burden tuberculosis countries in the world. The transitions from infection to clinical disease are very few signifying that host-defence factors could lead to the development of active disease. Toll-like receptor (TLR) 2 polymorphisms have been associated with regulation of TLR expression and development of active TB. In this study, blood samples of 187 subjects including 100 healthy and 87 TB positive were collected from three districts of Pakistan. DNA was extracted from blood and TLR 2 (-196 to -174del) polymorphism was analysed by polymerase chain reaction (PCR). The results suggest that the frequency of -196 to -174del/del polymorphism of TLR2 was significantly higher in TB-positive patients compared with healthy. Results revealed that (-196 to -174del) polymorphism may increase the susceptibility to TB in healthy population of Pakistan. Moreover, males with heterozygous genotype (I/D) are more prone to TB than females with the same genotype. The occurrence of TB infection has been found positively associated with the age, suggesting that the population within the range of 21-45 years is more susceptible to Mycobacterium tuberculosis than other age groups studied. A significant association is also observed between smoking and the chances of developing TB, confirming that smoking strongly promotes its incidence.