Cambridge Institute for Medical Research. Cambridge, UK / University of Leeds. School of Biology. Leeds, UK.University of Leeds. School of Biology. Leeds, UK.Southampton General Hospital. Southampton, UK.Cambridge Institute for Medical Research. Cambridge, UK.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil / São Paulo University. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Cambridge Institute for Medical Research. Cambridge, UK.Previous analyses indicate major gene control of susceptibility to leprosy per se and the HLA class II region has been
implicated in determining susceptibility and control of clinical phenotype. Segregation analysis using data from 76 Brazilian
leprosy multi-case pedigrees (1166 individuals) supported a two locus model as the best fit: a recessive major gene and a
recessive modifier gene(s) (single locus vs two locus model, P = 0.0007). Combined segregation and linkage analysis to
the major locus, showed strong linkage to HLA class II (HLA-DQB1 P = 0.000002, HLA-DQA1 P = 0.000002, HLA-DRB1
P = 0.0000003) and tumour necrosis factor genes (TNF P = 0.00002, LTA P = 0.003). Extended transmission disequilibrium
testing, using multiple affected family members, demonstrated that the common allele TNF*1 of the −308 promoter region
polymorphism showed linkage and/or association with disease per se, at a high level of significance (P , 0.0001). Two
locus transmission disequilibrium testing suggested susceptibility (TNF*1/LTA*2) and protective (TNF*2/LTA*2) haplotypes
in the class III region. Taken together the segregation and HLA analyses suggest the possibility of more than one
susceptibility locus in the MH
