RESUMEN
There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Neoplasias/genética , Tuberculosis/genética , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/patología , Población Negra/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Polimorfismo de Nucleótido Simple , Tuberculosis/tratamiento farmacológico , Tuberculosis/patología , Población Blanca/genéticaRESUMEN
We have assessed the utility of two new methods; dot-blot and bacteriophage replication techniques; for use in a routine diagnosis laboratory in poor resource settings in the screening of drug resistant Mycobacteria tuberculosis by comparing with the conventional proportion method. A total of 145 M. tuberculosis clinical isolates were tested for resistance to rifampicin; isoniazid; streptomycin and ethambutol. The dot blot had sensitivities of 91.7; 100; 93.5and 85.7 and specificities of 99.2; 99.2; 99.1and 99.2 for rifampicin; streptomycin; isoniazid and ethambutol; respectively. The phage technique had sensitivities of 92and 84.6and specificities of 99.2and 99.2for rifampicin and streptomycin; respectively. Both techniques yielded results within 48 hours of receipt of the culture on solid media.The high sensitivity and specificity coupled with rapidity of results indicate that these methods are potentially useful tools for screening resistance to anti-tuberculosis drugs in our setting. However; the phage replication technique; which is simpler and technically less demanding; seems the most suitable for routine screening of drug resistant mycobacteria in resource deprived countries such as Tanzania. We are recommending further field evaluation of the phage replication method so that it can complement; and possibly replace; the conventional proportion method in drug susceptibility testing
