Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island.

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.