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Résumé: En dépit d’un réservoir naturel de Mycobacterium leprae limité à l’homme et de la mise à disposition gratuite d’une antibiothérapie efficace, plus de 200 000 personnes développent la lèpre chaque année. Cette maladie demeure une cause majeure de handicaps et de stigmatisation sociale dans le monde. La cause de cette incidence constante est inconnue et indique que des aspects importants de la relation complexe entre l’agent pathogène et son hôte humain restent à découvrir. Une contribution importante de la génétique de l’hôte humain dans la susceptibilité à la lèpre a depuis longtemps été suggérée pour expliquer l’extrême variabilité observée entre les individus exposés de façon prolongée à l’agent pathogène. Devant l’impossibilité de cultiver M. leprae in vitro et en l’absence de modèle animal pertinent, la génétique épidémiologique est le principal outil utilisé pour identifier les gènes et les cascades immunologiques impliqués dans l’immunité protectrice contre M. leprae. Les études pangénomiques récentes ont permis d’identifier des voies physiopathologiques résolument nouvelles dont l’importance commence seulement à être comprise. De plus, ce prisme de la génétique humaine a placé la lèpre au carrefour d’autres pathologies comme la maladie de Crohn, l’asthme ou l’infarctus du myocarde. Ainsi la lumière sur la pathogenèse de nombreuses affections communes pourrait finalement surgir de la compréhension fine d’une maladie de l’ombre et lui bénéficier dans un juste retour des choses. [ABSTRACT FROM AUTHOR]

Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major public health problem worldwide, resulting in 8.7 million new cases and 1.4 million deaths each year. One third of the world''s population is exposed to M. tuberculosis and, after exposure, most, but not all, individuals become infected. Among infected subjects, only a minority (∼10%) will eventually develop clinical disease, which is typically either a primary, often extra-pulmonary, TB in children, or a reactivation, pulmonary TB in adults. Considerable genetic epidemiological evidence has accumulated to support a major role for human genetic factors in the development of TB. Numerous association studies with various candidate genes have been conducted in pulmonary TB, with very few consistent results. Recent genome-wide association studies revealed only a modest role for two inter-genic polymorphisms. However, a first major locus for pulmonary TB was mapped to chromosome 8q12-q13 in a Moroccan population after a genome-wide linkage screen. Using a similar strategy, two other major loci controlling TB infection were recently identified. While the precise identification of these major genes is ongoing, the other fascinating observation of these last years was the demonstration that TB can also reflect a Mendelian predisposition. Following the findings obtained in the syndrome of Mendelian susceptibility to mycobacterial diseases, several children with complete IL-12Rβ1 deficiency, were found to have severe TB as their sole phenotype. Overall, these recent findings provide the proof of concept that the human genetics of TB involves a continuous spectrum from Mendelian to complex predisposition with intermediate major gene involvement. The understanding of the molecular genetic basis of TB will have fundamental immunological and medical implications, in particular for the development of new vaccines and treatments. [Copyright &y& Elsevier]

Abstract: Objectives: The study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD). Patients and methods: We focused our study on two samples originating from the Tunisian centre: 318 healthy controls and 90 patients suffering from COPD. Data analysis was investigated by AAT level quantification, serum isoelectric focusing (IEF) and RFLP-PCR performed with PiS and PiZ allele specific primers. Results: We calculated PiM1, PiM2, PiM3, PiS and PiZ allele frequencies in patients and controls. The difference in allele frequencies is significant only for the PiM2 allele (P =0.00378). In COPD patients, we note the presence of PiZ allele. This allele mainly observed in European populations, is rare in Subsharian populations and not described in North Africa. Conclusion: PiZ allele is found in COPD sample and never in Tunisian controls. However, no significant difference in PiZ allele frequency between patients and controls can be concluded. PiM2 allele, which is considered as “normal” variant can be associated with COPD risk. [Copyright &y& Elsevier]