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Licensed Unlicensed Requires Authentication Published by De Gruyter August 21, 2015

The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis

  • Yvain Salinas-Delgado , Carlos Galaviz-Hernández , René García Toral , Carmen A. Ávila Rejón , Miguel A. Reyes-Lopez , Antonio Rojas Martínez , Gerardo Martínez-Aguilar and Martha Sosa-Macías EMAIL logo


Background: Polymorphisms in SLC11A1/NRAMP1 have shown an important association with susceptibility to tuberculosis and progression to active disease. However, whether there is an association of these polymorphisms with treatment failure is unknown. The aim of this study was to determine the association of SLC11A1 polymorphisms with treatment failure in Mexican subjects with pulmonary tuberculosis.

Methods: Thirty-three subjects with treatment failure were paired by age and body mass index with 33 patients who successfully completed treatment and were considered cured. We assessed the polymorphisms of SLC11A1 in the regions of D543N and INT4 via polymerase chain reaction real-time TaqMan® single nucleotide polymorphism (SNP) genotyping.

Results: We found that D543N (G/A genotype) was associated with treatment failure in patients with pulmonary tuberculosis [odds ratio (OR) 11.61, 95% confidence interval (CI) 3.66–36.78]. When adjusted by gender, this association remained significant in males (OR 11.09, 95% CI 3.46–35.51).

Conclusions: In our male population, the presence of the D543N polymorphism of SLC11A1 is a risk factor for treatment failure. This finding should be confirmed in other populations.

Corresponding author: Martha Sosa-Macías, Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional del Instituto Politécnico Nacional, Durango PC, México, Phone: +52 618 8142091, Fax: +52 618 8144550, E-mail:


This work was supported by the SIP-IPN Project (20144307), FONSEC-CONACYT Project (162368), and the “Comisión de Operación y Fomento de Actividades Académcas” from the Instituto Politecnico Nacional (CG-H and MS-M). We thank the physicians of the participating hospitals that provided the facilities to carry out the clinical work. We thank the Department of Epidemiology of the Ministry of Health and IMSS Durango and Veracruz. We wish to thank CONACYT-Mexico for the scholarship granted to Yvain Salinas-Delgado.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. CENAPRECE. Datos y retos en tuberculosis fármacorresistente en México. 18 Curso de actualización en el diagnóstico y tratamiento de la tuberculosis en el niño y el adulto. Secretaria de salud. Junio 2014. Available at: in Google Scholar

2. Narasimhan P, Wood J, Macintyre CR, Mathai D. Risk factors for tuberculosis. Pulm Med 2013;2013:828939.10.1155/2013/828939Search in Google Scholar PubMed PubMed Central

3. van Crevel R, Parwati I, Sahiratmadja E, Marzuki S, Ottenhoff TH, Netea MG, et al. Infection with Mycobacterium tuberculosis Beijing genotype strains is associated with polymorphisms in SLC11A1/NRAMP1 in Indonesian patients with tuberculosis. J Infect Dis 2009;200:1671–4.10.1086/648477Search in Google Scholar PubMed

4. Supek F, Superkova L, Nelson H, Nelson N. A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc Natl Acad Sci USA 1996;93:5105–10.10.1073/pnas.93.10.5105Search in Google Scholar PubMed PubMed Central

5. Li X, Yang Y, Zhou F, Zhang Y, Lu H, Jin Q, et al. SLC11A1 (NRAMP1) polymorphisms and tuberculosis susceptibility: updated systematic review and meta-analysis. PLoS One 2011;6:e15831.10.1371/journal.pone.0015831Search in Google Scholar PubMed PubMed Central

6. Zhang W, Shao L, Weng X, Hu Z, Jin A, Chen S, et al. Variants of the natural resistance-associated macrophage protein 1 gene (NRAMP1) are associated with severe forms of pulmonary tuberculosis. Clin Infect Dis 2005;40:1232–6.10.1086/428726Search in Google Scholar PubMed PubMed Central

7. Khalilullah SA, Harapan H, Hasan NA, Winardi W, Ichsan I, Mulyadi M. Host genome polymorphisms and tuberculosis infection: what we have to say? Egypt J Chest Dis Tubercul 2014;63:173–85.10.1016/j.ejcdt.2013.12.002Search in Google Scholar PubMed PubMed Central

8. Becerra MC, Freeman J, Bayona J, Shin SS, Kim JY, Furin JJ, et al. Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2000;4:108–14.Search in Google Scholar

9. Yoshiyama T, Yanai H, Rhiengtong D, Palittapongarnpim P, Nampaisan O, Supawitkul S, et al. Development of acquired drug resistance in recurrent tuberculosis patients with various previous treatment outcomes. Int J Tuberc Lung Dis 2004; 8:31–8.Search in Google Scholar

10. Yang C, Luo T, Sun G, Qiao K, Sun G, DeRiemer K, et al. Mycobacterium tuberculosis Beijing strains favor transmission but not drug resistance in China. Clin Infect Dis 2012;55:1179–87.10.1093/cid/cis670Search in Google Scholar PubMed PubMed Central

11. Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 2008;8:737–44.10.1038/nri2394Search in Google Scholar PubMed PubMed Central

12. Dooley KE, Lahlou O, Ghali I, Knudsen J, Elmessaoudi MD, Cherkaoui I, et al. Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco. BMC Public Health 2011;11:140.10.1186/1471-2458-11-140Search in Google Scholar PubMed PubMed Central

13. Ben-Selma W, Harizi H, Letaief M, Boukadida J. Age- and gender-specific effects on NRAMP1 gene polymorphisms and risk of development of active tuberculosis in Tunisian population. Int J Infect Dis 2012;16:e543–50.10.1016/j.ijid.2011.11.016Search in Google Scholar PubMed

Received: 2015-4-28
Accepted: 2015-7-22
Published Online: 2015-8-21
Published in Print: 2015-9-1

©2015 by De Gruyter

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