Association of NRAMP1-INT4 gene with Susceptibility to Tuberculosis in the Sudanese Population: A Case-Control Study

Abstract: Background: Sudan is a Sub-Saharan African country with a high prevalence rate of Tuberculosis. Natural Resistant Associated Macrophage Protein 1 (NRAMP1) plays a potential role in the development of immunity against TB, and it has a critical role in disease resistance. The aim of the study was to evaluate the association of NRAMP1 polymorphism at intron4 (INT4) region with susceptibility to TB infection. Methods: Demographic, clinical and microbiological data were collected from 150 participants and investigated using designed questionnaire. The genotyping of NRAMP1-INT4 polymorphism was performed in 60 TB-infected patients and 50 healthy control using Polymerase chain reaction and restriction fragment-length polymorphism method (PCR-RFLP). Results: Among cases (60%) were males, only (3.3%) were vaccinated. The most reported risk factors were tobacco smoking (17%), diabetes (10%), alcohol consumption (2%) and corticosteroid therapy intakes (1%). Pulmonary TB was detected in 67% of the patients, 24% had pulmonary/MDR and 9% had extrapulmonary TB. The frequency of wild G allele was significantly higher in cases compared with healthy control subjects (P-value <0.0001). Also, a significant association was observed between the heterozygosity for NRAMP1-INT4 variant and resistance to TB infection (P-value 0.001, OR= 4.83, 95%CI 1.96~11.88). Homozygotes mutant INT4 (C/C) genotype was not detected in both cases and controls. Conclusions: the NRAMP1-INT4 polymorphism may serve as marker of unidentified genetic factors that may play a critical role in host immunity to TB in the Sudanese population. Further studies with large sample size are recommended to determine population-specific genetic associations with TB susceptibility in order to guide TB therapy and prophylaxis in a population-specific manner. Keywords: M. tuberculosis, MDR, NRAMP1, SNP, Sudan.