Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

• Autor(a) principal: Peacock, C. S
• Data de Publicação: 2001
• Outros Autores: Collins, A, Shaw, M. - A, Silveira, Fernando Tobias, Costa, J, Coste, C. H, Nascimento, M. D, Siddiqui, R, Shaw, Jeffrey Jon, Blackwell, J. M
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/4367
• topic: Leishmaniose Visceral / parasitologia; Leishmaniose Visceral / epidemiologia; Leishmaniose Visceral / genética; Predisposição Genética para Doença / genética; Suscetibilidade a Doenças

Familial clustering of disease, racial differences in asymptomatic:disease ratios, and studies of mice all point to a genetic component for disease susceptibility in visceral leishmaniasis. Analysis of 87 multi-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for Leishmania chagasi demonstrates a high relative risk ratio (λ2S = 34) to further siblings of affected sibling pairs. Complex segregation analysis using POINTER and COMDS show that all single locus models, as well as polygenic and multifactorial models, provide a signficantly (P < 0.001) better fit to the data than a sporadic model. Of the genetic models, the general single locus model was not significantly different from additive or dominant single locus models, all of which gave a gene frequency for the putative disease susceptibility allele of ∼0.002. The general single locus model was strongly favored (P < 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (P < 0.001 in all cases) in favor of the general single locus model. Using COMDS, the analysis was extended to consider two locus models. Results under a general two-locus model did not differ significantly from the dominant, additive, or general single locus models. Under this model, one locus was estimated at a gene frequency of 0.0017, i.e., in the same range as the disease susceptibility locus for the most favored single gene models, with the second locus at a much lower frequency of 0.0002. Hence, the data support the hypothesis that a single major gene may be important in determining disease susceptibility in this population. To identify the gene(s) involved, a genome scan with replication using two subsets of these larger pedigrees with power to detect linkage is in progress.