Comparison of Nramp1 Gene Polymorphism among TB Health Care Workers and Recently Infected Cases; Assessment of Host Susceptibility

Authors

1 Mycobacteriology Research Center,

2 Mycobacteriology Research Center

3 Department of Infectious Disease

4 Department of Clinical Anatomical Pathology

5 Lung Transplantation Research Center

6 Department of Clinical Anatomical Pathology,

7 Department of Pulmonary Medicine,

8 Department of Pediatrics, NRITLD, Shahid Beheshti University M.C., TEHRAN-IRAN

Abstract

Background: A link between polymorphisms in the natural resistance –associated macrophage protein gene 1 (Nramp) and susceptibility to tuberculosis (TB) has been demonstrated worldwide. This study aimed to investigate the Nramp1 gene variants among workers exposed to TB bacilli (1-2 hours per day for 1 to 20 years) who did not develop the diseases with those who developed the disease through recent transmission. Materials and Methods: The polymorphism of Nramp1 at INT4, D543 and 3'UTR was examined in 71 newly smear-positive TB cases and 39 healthcare workers exposed to TB. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to genotype Nramp1 polymorphism. Patients' clinical and demographical data were collected. Results: The heterozygote patterns of INT4 (G/C), D543 (G/A) and 3'UTR (+/del) occurred more frequently in control subjects than in patients (P =0.012), respectively (odds: 1.9 CI95%) [1.13-3.12]. Although, the homozygous patterns of INT4 (C/C; 8.5%), D543 (A/A; 1.4%) and 3'UTR (del/del; 1.4%) were only seen in patients (sensitivity 11% and specificity 100%). The other risk factors like gender, age, resistance and PPD were not associated with Nramp1 gene polymorphism. Conclusion: Individuals with homozygous type mutation have an increased risk of developing tuberculosis. Therefore, we suggest detection of Nramp1 variants in high-risk groups i.e., health workers and close contact cases. (Tanaffos 2008; 7(1): 19-24)

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