Leprosy, a chronic
infectious disease caused by
Mycobacterium leprae,
affects an estimated 700,000
persons each year. Clinically,
leprosy can be categorized as paucibacillary or multibacillary
disease. These clinical forms develop in
persons that are intrinsically susceptible to
leprosy per se, that is,
leprosy independent of its specific clinical manifestation. We
report here on a
genome-wide search for loci controlling susceptibility to
leprosy per se in a panel of 86
families including 205
siblings affected with
leprosy from Southern
Vietnam. Using model-free linkage
analysis, we found significant evidence for a susceptibility
gene on
chromosome region 6q25 (maximum likelihood binomial (MLB)
lod score 4.31; P = 5 x 10(-6)). We confirmed this by
family-based
association analysis in an independent panel of 208
Vietnamese leprosy simplex
families. Of seven
microsatellite markers underlying the linkage peak,
alleles of two markers (D6S1035 and D6S305) showed strong evidence for
association with
leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively).