RESUMO
Despite recent advances revealing genetic factors influencing caries susceptibility, questions regarding the model of inheritance involved are yet to be addressed. We conducted a Complex Segregation Analysis on decayed teeth in a sample of homogenous, isolated families recruited from the Brazilian Amazon. A dominant, major gene effect controlling resistance to phenotype was detected. The frequency of the resistance allele "A" was 0.63; mean numbers of decayed teeth were 1.53 and 9.53 for genotypes AA/AB and BB, respectively. These results represent a step toward a description of the exact nature of the genetic risk factors controlling human susceptibility to caries.
Assuntos
Suscetibilidade à Cárie Dentária/genética , Cárie Dentária/genética , Adolescente , Adulto , Brasil , Índice CPO , Feminino , Frequência do Gene , Genes Dominantes , Predisposição Genética para Doença , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Variações Dependentes do Observador , Linhagem , Adulto JovemRESUMO
Each year an estimated 600000 new leprosy cases are diagnosed worldwide. The spectrum of the disease varies widely from limited tuberculoid forms to extensive lepromatous forms. A measure of the risk to develop lepromatous forms of leprosy is provided by the extent of skin reactivity to lepromin (Mitsuda reaction). To address a postulated oligogenic control of leprosy pathogenesis, we investigated in the present study linkage of leprosy susceptibility, leprosy clinical subtypes, and extent of the Mitsuda reaction to six chromosomal regions carrying known or suspected leprosy susceptibility loci. The only significant result obtained was linkage of leprosy clinical subtype to the HLA/TNF region on human chromosome 6p21 (P(corrected)=0.00126). In addition, we established that within the same family different HLA/TNF haplotypes segregate into patients with different leprosy subtypes directly demonstrating the importance of this genome region for the control of clinical leprosy presentation.
Assuntos
Masculino , Feminino , Humanos , Antígenos HLA/genética , /genética , Fator de Necrose Tumoral alfa/genética , Genótipo , Hanseníase/classificação , Hanseníase/genética , Ligação Genética/genética , Predisposição Genética para Doença , Fenótipo , LinhagemRESUMO
Humans are exposed worldwide to a variety of environmental mycobacteria (EM) and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. Although rarely pathogenic, poorly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. M. tuberculosis and M. leprae are more virulent, causing tuberculosis, and leprosy, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. There is now accumulating evidence that the large interindividual variability of clinical outcome results in part from variability in the human genes that control host defense. We review here in current knowledge about genetic predisposition to common (leprosy and tuberculosis) and rare (BCG and EM infections) mycobacterial infections.
Assuntos
Humanos , Hanseníase/etiologia , Hanseníase/genética , Infecções por Mycobacterium/etiologia , Infecções por Mycobacterium/genética , Mycobacterium/patogenicidade , Predisposição Genética para Doença , Tuberculose Pulmonar/etiologia , Tuberculose Pulmonar/genética , Variação GenéticaRESUMO
The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.
Assuntos
Masculino , Feminino , Humanos , Antígeno de Mitsuda/imunologia , China/etnologia , Granuloma , Hanseníase Tuberculoide/imunologia , Hanseníase Virchowiana/imunologia , Hanseníase/imunologia , Pele/imunologia , Vietnã , Fenótipo , Haplótipos , Imunidade Inata , Injeções Intradérmicas , Linfócitos T Auxiliares-Indutores , Linhagem , Núcleo FamiliarRESUMO
Tegumentary leishmaniasis due to Leishmania braziliensis is a parasitic disease that occurs in two stages after the infected sandfly bite: (1) a primary cutaneous lesion followed by (2) a secondary mucosal involvement generally resulting in severe facial deformities. In order to investigate the genetic and environmental factors involved in the development of the cutaneous lesion, a familial study was performed in a region of Bolivia in which the disease is endemic. Complete selection of 118 nuclear families (703 subjects, with 241 patients), each with at least one cutaneous affected subject, was achieved; 41 families were of native origin, and 77 (herein designated "migrant") recently had settled in the area. For the analysis, the trait under study was the time to onset of the primary cutaneous lesion. The start of the follow-up was birth, for native population, or date of arrival in the endemic area, for migrant population. Segregation analysis was performed by use of a model based on survival analysis methods that allows joint estimation of genetic and environmental effects and accounts for gene x covariate interactions. A significant effect of gender, home-forest distance, and forest-related activity was found. In the 77 migrant families there was evidence for a recessive major gene controlling the onset of the primary cutaneous lesion, with residual familial dependences and age x genotype interaction. Penetrance estimations show that young subjects are genetically more susceptible than older subjects, suggesting that this genetic component could concern mechanisms involved in the development of individual protection during childhood. There was also a significant genetic heterogeneity of the sample according to the native/migrant origin of the families, and no major-gene effect was found in the native subsample.
Assuntos
Leishmania braziliensis , Leishmaniose Cutânea/genética , Adulto , Fatores Etários , Animais , Bolívia , Criança , Suscetibilidade a Doenças , Feminino , Humanos , Indígenas Sul-Americanos/genética , Leishmaniose Cutânea/epidemiologia , Leishmaniose Tegumentar Difusa/genética , Leishmaniose Mucocutânea/genética , Masculino , Núcleo Familiar , Probabilidade , Fatores de Tempo , MigrantesRESUMO
A survival analysis was performed on data from an endemic area of Bolivia where two populations, natives and highland migrants, were living, to investigate risk factors for onset of cutaneous leishmaniasis (CL) and its mucosal form (MCL). In a first data set (703 subjects with 242 CL patients), significant risk factors for CL were gender, native/migrant status, activity, and home-forest distance. The instantaneous risk of CL increased until adolescence in both populations, and rapidly decreased thereafter. This risk was 3-10 times higher in migrants than in natives until 20 years of age, and became similar thereafter. Environmental and behavioral factors did not seem sufficient to explain this contrast between the two populations, and this evolution with age may suggest differences in the mechanisms involved in the development of individual protection during childhood. In a second data set (446 CL patients with 34 mucosal forms) the native/migrant status was the main factor associated with the onset of mucosal form.