Genetic epidemiology of visceral leishmaniasis in northeastern Brazil
Peacock, C. S
Shaw, M. - A
Silveira, Fernando Tobias
Coste, C. H
Nascimento, M. D
Shaw, Jeffrey Jon
Blackwell, J. M
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.
xmlui.dri2xhtml.METS-1.0.item-citationPEACOCK, C. S. et al. Genetic epidemiology of visceral leishmaniasis in northeastern Brazil. Genetic Epidemiology, v, 20,n. 3, p. 383-396, Apr. 2001.
xmlui.dri2xhtml.METS-1.0.item-decsPrimaryLeishmaniose Visceral / parasitologia
Leishmaniose Visceral / epidemiologia
Leishmaniose Visceral / genética
Predisposição Genética para Doença / genética
Suscetibilidade a Doenças