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 extra-pulmonary 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.