Drug Metabol Pers Ther 2015; 30(3): 211–214 *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: msosam@ipn.mx Yvain Salinas-Delgado and Carlos Galaviz-Hernández: Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional del Instituto Politécnico Nacional, Durango PC, México René García Toral: Instituto Mexicano del Seguro Social UMAE Hospital de Especialidades No. 14, Veracruz PC, México Carmen A. Ávila Rejón: Hospital Regional de Alta Especialidad, SS, Veracruz PC, México Miguel A. Reyes-Lopez: Laboratorio de Medicina de Conservación, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, Tamaulipas PC, México Antonio Rojas Martínez: Servicios de Salud de Durango, SS, Durango PC, México Gerardo Martínez-Aguilar: Jefatura de Prestaciones Médicas, Instituto Mexicano del Seguro Social, Durango PC, México 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* The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis DOI 10.1515/dmpt-2015-0019 Received April 28, 2015; accepted July 22, 2015; previously published online August 21, 2015 Abstract 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 polymor- phisms 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 suc- cessfully 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 asso- ciated with treatment failure in patients with pulmonary tuberculosis [odds ratio (OR) 11.61, 95% confidence inter- val (CI) 3.66–36.78]. When adjusted by gender, this asso- ciation 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 treat- ment failure. This finding should be confirmed in other populations. Keywords: pulmonary tuberculosis; SLC11A1/NRAMP1; treatment failure. Introduction Tuberculosis (TB) remains one of world’s deadliest infec- tious diseases. However, the World Health Organization (WHO) estimates that most deaths from TB are prevent- able with early recognition and appropriate treatment. The growth of Mycobacterium tuberculosis (MTB) is usually inhibited by the development of an effective immune response. Therefore, only approximately 10% of infected subjects will eventually develop clinical disease. In 2013 in Mexico, there were 19,738 new cases of pulmonary TB (PTB). In the states, where this study was performed, approximately 1300 naïve treatment subjects received therapy, which failed in 58 subjects [1]. The progression of PTB is strongly associated with immunosuppression. However, this is not a universal finding, suggesting that other factors, both environmen- tal and host dependent, are involved [2]. The latter case is exemplified by the MTB Beijing genotype, which is strongly associated with polymorphisms in the SLC11A1/ NRAMP1 gene [3]. The SLC11A1-encoded product is an integral mem- brane protein that is exclusively expressed in the lysoso- mal compartment of monocytes and macrophages, acting as a pump for divalent cations (Fe 2+ and Mn 2+ ) from the extracellular milieu into the cytoplasm of a macrophage. Brought to you by | Instituto Politecnico Nacional Authenticated Download Date | 7/9/18 5:02 PM