RESUMO
Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed.
Assuntos
Genes Dominantes/genética , Esquistossomose mansoni/genética , Fatores Etários , Brasil , Predisposição Genética para Doença , Humanos , Contagem de Ovos de Parasitas , Linhagem , Fenótipo , Esquistossomose mansoni/transmissão , Fatores SexuaisRESUMO
Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.
Assuntos
Ligação Genética , Marcadores Genéticos , Hanseníase Virchowiana/genética , Hanseníase/genética , Sistema ABO de Grupos Sanguíneos/genética , Suscetibilidade a Doenças , Antígenos HLA/genética , Humanos , Alótipos de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/genética , Sistema do Grupo Sanguíneo Rh-Hr/genética , Índias OcidentaisRESUMO
To determine the nature of the genetic component controlling susceptibility to leprosy and its subtypes, complex segregation analysis, by means of the POINTER strategy, was performed on 27 multigenerational pedigrees from Desirade, a Caribbean island where leprosy is highly prevalent. The results are consistent with the presence of a recessive or codominant major gene controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Under the major-gene model, tests of homogeneity to check for internal consistency of the sample and to compare subsamples according to an epidemiological criterion, the place of residence of the probands, were conducted; results of none of these tests were significant. However, we have noted that information on 3 generations (nuclear families with a pointer to the sibship) is of major importance for detecting major gene(s). Besides, the discrepancy in the results obtained in separate analyses of the family subsamples defined by the place of residence of the probands is discussed in terms of possible genetic and/or environmental differences. Referring to experimental data and previous studies, we suggest that the gene for susceptibility to leprosy per se and that for susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.
Assuntos
Hanseníase/genética , Modelos Genéticos , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Linhagem , Probabilidade , Índias OcidentaisRESUMO
A relationship between markers related to the immune response (HLA system, Gm and Km immunoglobulin allotypes) and susceptibility to cutaneous leishmaniasis was investigated in a population of Hmong refugees who had recently settled in French Guiana. Two approaches were used: 1) case/control comparisons of the marker phenotype distribution to detect possible associations; 2) multiple-case family studies to search for marker-linked genes. When the distribution of HLA-A, B, C, antigens and Gm, Km allotypes was compared between patients and controls, only a significant decrease of HLA-Cw7 antigen among leishmaniasis patients was detected (p = 0.01). No interaction between any two of these markers and the disease was found. On the other hand, neither an HLA, Gm or Km susceptibility gene could be demonstrated in the informative sets of affected siblings. These results are discussed with respect to those reported in other infectious diseases.
Assuntos
Antígenos HLA/genética , Alótipos de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/genética , Leishmaniose/genética , Suscetibilidade a Doenças , Guiana Francesa , Frequência do Gene , Marcadores Genéticos , Haplótipos , Humanos , Laos/etnologia , Leishmaniose/etnologia , FenótipoRESUMO
Hearing troubles were found to be very frequent among inhabitants of French origin in a small Caribbean island. Segregation analysis of hearing loss was performed in 165 complete nuclear families and revealed that familial aggregation could be entirely explained by a single recessive gene with high frequency (0.40). Homozygous individuals for this gene would probably be more susceptible to ototoxic agents than other individuals. High frequency of this gene may be due to a founder effect.