Age- and gender-specific effects on NRAMP1 gene polymorphisms and risk of the development of active tuberculosis in Tunisian populations

Abstract

Studies that have assessed NRAMP1 polymorphisms and their association with susceptibility to tuberculosis (TB) in humans have yielded conflicting results. In this study, we evaluated the association between NRAMP1 gene polymorphisms and the risk of the development of active TB in Tunisian populations. The distribution of 3'-UTR and D543N polymorphisms in 223 TB patients (168 patients with pulmonary TB (PTB) and 55 patients with extrapulmonary TB (EPTB)) and 150 healthy donors was determined by PCR-restriction fragment length polymorphism (RFLP) method. We found that AA and AG genotypes appeared to be associated with susceptibility to PTB (odds ratio (OR) 10.8, 95% confidence interval (CI) 1.37-230.8; p corrected for the number of genotypes (pc)=0.018) and EPTB (OR 4.37, 95% CI 1.64-11.82; pc=0.0024), respectively, in patients aged less than 30 years. However, wild-type GG genotype appeared to be associated with resistance against PTB in females (OR 0.1, 95% CI 0.01-0.74; pc=0.03). The 3'-UTR del/del genotype appeared to be associated with susceptibility to PTB in patients aged less than 30 years (OR 3.75, 95% CI 1.5-9.52; pc=0.003). In contrast, TGTG+/del might be associated with resistance against the development of active PTB (OR 0.23, 95% CI 0.08-0.65; pc=0.003). A-del haplotype appeared to be associated with susceptibility to PTB (OR 1.79, 95% CI 1.11-2.9; pc=0.04). Collectively, our results suggest an association of NRAMP1 3'-UTR and D543N polymorphisms with susceptibility to mycobacterial infection in Tunisian populations in relation to age and sex.