Leprosy is a chronic infectious disease that is still a major global health problem with 700,000 new cases occurring each year. The disease presents itself in different clinical manifestations, ranging from single lesion paucibacillary to severe, multiple lesion multibacillary forms. In order to identify genomic regions linked with susceptibility to leprosy, we performed a genome-wide scan in families from South Vietnam. These families contain both paucibacillary and multibacillary cases allowing for the genetic analysis of susceptibility to leprosy ''per se'' and leprosy type. A total of 87 multiplex families were genotyped for 395 highly informative microsatellite markers spanning the entire human genome. Genetic model-free linkage analysis, using the Maximum Likelihood Binomial (MLB) method initially pointed to 11 genomic regions showing suggestive evidence for linkage with either leprosy per se or leprosy type (MLB lod score41.5). Analysis of the high density marker maps (information content 495%) revealed strong evidence for linkage between one chromosomal region and leprosy ''per se'' (MLB lod score of 4.21; p ΒΌ 5.10-6). Microsatellite markers located in the same region have been used to replicate this result in a familybased association study using an independent sample of 208 simplex Vietnamese pedigrees (p ΒΌ 6.10-5). In addition, the HLA region presented an MLB lod score of 2.62 (p ΒΌ 2.10-4) when tested for leprosy ''per se'' and 2.64 when tested for leprosy type. These results strongly suggest the existence of at least one major locus for the control of susceptibility to leprosy ''per se''. They are also in accordance with the generally accepted idea of a role for the HLA region in controlling disease susceptibility and clinical form of leprosy disease.
IGES-2
A locus on chromosome 2 influences levels of tissue factor pathway inhibitor: results from the GAIT study