MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3' UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58-1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.

[Tuberculosis treatment. A practical guide elaborated by the tuberculosis section, Argentine Association of Respiratory Medicine]. / Tratamiento de la tuberculosis. Guia practica elaborada por la seccion tuberculosis, Asociacion Argentina de Medicina Respiratoria.

Tuberculosis is a worldwide prevalent disease. The emergence of multidrug-resistant strains spurred the search for new drugs. There are several tuberculosis treatment guidelines, international and local in a programmatic approach. An Argentinean specialists panel draw practical guidelines based in clinical criteria and the local and international bibliography through consensus meetings, including issues as: antituberculosis drugs available in Argentina, initial and re-treatement modalities, special situations treatment, adverse reactions to antituberculosis drugs, current indications of surgical treatment and new drugs under study for the treatment of the disease.

Tratamiento de la tuberculosis: guia practica elaborada por la Seccion Tuberculosis, Asociacion Argentina de Medicina Respiratoria / Tuberculosis treatment: a practical guide elaborated by the Tuberculosis Section, Argentine Association of Respiratory Medicine

La tuberculosis es una enfermedad prevalente en todo el mundo. La emergencia de cepas multirresistentes del Mycobacterium tuberculosis ha incentivado la búsqueda de nuevos fármacos. Existen diversas guías de tratamiento de la enfermedad, internacionales y a nivel programático local. Un grupo de especialistas argentinos elaboró una guía práctica basada en criterios clínicos y en la bibliografía nacional e internacional sobre el tema a través de reuniones de consenso, abarcando tópicos como: fármacos antituberculosos disponibles en la Argentina, modalidades de tratamiento inicial y retratamiento, tratamiento en situaciones especiales, reacciones adversas a fármacos antituberculosos, indicaciones actuales de tratamiento quirúrgico y nuevos fármacos en estudio para el tratamiento de la enfermedad.(AU)

Tuberculosis is a worldwide prevalent disease. The emergence of multidrug-resistant strains spurred the search for new drugs. There are several tuberculosis treatment guidelines, international and local in a programmatic approach. An Argentinean specialists panel draw practical guidelines based in clinical criteria and the local and international bibliography through consensus meetings, including issues as: antituberculosis drugs available in Argentina, initial and re-treatement modalities, special situations treatment, adverse reactions to antituberculosis drugs, current indications of surgical treatment and new drugs under study for the treatment of the disease.(AU)

Tratamiento de la tuberculosis: guia practica elaborada por la Seccion Tuberculosis, Asociacion Argentina de Medicina Respiratoria / Tuberculosis treatment: a practical guide elaborated by the Tuberculosis Section, Argentine Association of Respiratory Medicine

La tuberculosis es una enfermedad prevalente en todo el mundo. La emergencia de cepas multirresistentes del Mycobacterium tuberculosis ha incentivado la búsqueda de nuevos fármacos. Existen diversas guías de tratamiento de la enfermedad, internacionales y a nivel programático local. Un grupo de especialistas argentinos elaboró una guía práctica basada en criterios clínicos y en la bibliografía nacional e internacional sobre el tema a través de reuniones de consenso, abarcando tópicos como: fármacos antituberculosos disponibles en la Argentina, modalidades de tratamiento inicial y retratamiento, tratamiento en situaciones especiales, reacciones adversas a fármacos antituberculosos, indicaciones actuales de tratamiento quirúrgico y nuevos fármacos en estudio para el tratamiento de la enfermedad.

Tuberculosis is a worldwide prevalent disease. The emergence of multidrug-resistant strains spurred the search for new drugs. There are several tuberculosis treatment guidelines, international and local in a programmatic approach. An Argentinean specialists panel draw practical guidelines based in clinical criteria and the local and international bibliography through consensus meetings, including issues as: antituberculosis drugs available in Argentina, initial and re-treatement modalities, special situations treatment, adverse reactions to antituberculosis drugs, current indications of surgical treatment and new drugs under study for the treatment of the disease.