Genetic epidemiology of the susceptibility to leprosy.

Abstract

To test the hypothesis that genetic factors are operative in the predisposition to leprosy (Hansen's disease) in humans, a genetic epidemiologic investigation was performed on 269 leprosy kindreds containing 552 affected individuals from an isolated population in Papua New Guinea. The community, and not the family, was the basic social unit. Leprosy, an infectious disease, was not communal but strongly familial within the Karimui.Segregation analysis, to determine whether a major gene for the susceptibility to leprosy was segregating within a single multigenerational kindred, could not differentiate between a Mendelian genetic and a purely environmental hypothesis. The composite kindred data, however, suggest a genetic hypothesis for the nonimmunologically induced susceptibility to leprosy per se. Within familial kindreds leprosy invariably emanated from a common ancestral sibship, and risk was associated with the closeness of kin but not with infectivity or severity.

Interferon-Gamma Receptor-1 Gene Promoter Polymorphisms and Susceptibility to Leprosy in Children of a Single Family

“…1 Clinically, leprosy is manifested as a disease spectrum with two polar forms, lepromatous-LL and tuberculoid-TT. 2 The spectrum is further divided into infectious multibacillary, paucibacillary, and transitional borderline forms. 2 The precise mechanism of transmission of Mycobacterium leprae is unknown.…”

“…2 The spectrum is further divided into infectious multibacillary, paucibacillary, and transitional borderline forms. 2 The precise mechanism of transmission of Mycobacterium leprae is unknown. Recent molecular studies have begun to explain the importance of immune response to M. leprae at two fundamental levels.…”

“…3,4 Generally, they revealed a predominance of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) transcripts in tuberculoid lesions, and IL-4, IL-5, and IL-10 in lepromatous ones. 2,3 Alternatively, in cytokine genes several single nucleotide polymorphisms (SNPs) have been confirmed to play a critical role in triggering host-pathogen interactions. 5 In this study, the influence of major candidate genes, i.e., SNPs in the natural resistanceassociated macrophage protein 1 ( NRAMP1 ) gene, vitamin D receptor (VDR), TNF-α, IL-10, interleukin-12-receptor 1 (IL-12R1), and IFNGR1 were investigated within infected children of a single family.…”

“…10,12 Generally, the diverse genetic results of the disease acquisition might be explained by distinct genetic susceptibly to the disease among different populations. 2 Clearly, the complete absence of IFNGR1 on cell surface induces so profound an immune defect that such mutations are unlikely to explain M. leprae susceptibility in the general population. However, the existence of heterozygous carriers of the defect or more subtle variations in this gene might explain differences in M. leprae susceptibility within the population.…”

La lèpre

“…< que certains facteurs génétiques vont influencer le risque d'infection lors d'une exposition prolongée à M. leprae (hypothèse difficile à valider en l'absence de mesure suffisamment sensible de l'infection asymptomatique), d'autres la susceptibilité à la lèpre per se (c'est-à-dire la maladie indépendamment de sa forme clinique), et d'autres encore la polarisation vers une forme clinique particulière (Figure 1). Les études d'agrégation familiale ont observé une prévalence accrue de lèpre chez les individus apparentés à des patients lépreux [9] et des études de jumeaux ont retrouvé un taux de concordance pour la lèpre de 60 à 85 % chez les jumeaux monozygotes contre seulement 15-20 % chez les jumeaux dizygotes [10][11][12]. Plusieurs analyses de ségrégation ont ensuite mis en évidence une forte composante familiale influençant la lèpre per se et ses sous-types [13,14].…”