The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis.
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.
Yvain
Y
Salinas-Delgado
Carlos
C
Galaviz-Hernández
René García
RG
Toral
Carmen A
CA
Ávila Rejón
Miguel A
MA
Reyes-Lopez
Antonio Rojas
AR
Martínez
Gerardo
G
Martínez-Aguilar
Martha
M
Sosa-Macías
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D017211:Treatment Failure; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D000099173:Natural Resistance-associated Macrophage Protein 1
D000995:Antitubercular Agents; D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1