Susceptibility to Leprosy Is Linked to the Human<i>NRAMP1</i>Gene

TLDR

Leprosy is a debilitating skin and nerve disease in which host genetics play a key role, and the human NRAMP1 gene is a candidate susceptibility locus because its mouse homolog controls resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were genotyped for NRAMP1 alleles and four linked polymorphic markers, from which highly informative haplotypes overlapping NRAMP1 were constructed and their segregation into leprosy‑affected offspring analyzed. The segregation of NRAMP1 haplotypes into affected siblings was significantly nonrandom, supporting the hypothesis that NRAMP1 itself is a leprosy susceptibility locus.

Abstract

Leprosy is a debilitating infectious disease of human skin and nerves. Genetic factors of the host play an important role in the manifestation of disease susceptibility. The human NRAMP1 gene is a leprosy susceptibility candidate locus since its murine homologue Nramp1 (formerly Lsh/Ity/Bcg) controls innate resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were genotyped for NRAMP1 alleles and 4 closely linked polymorphic markers. Highly informative haplotypes overlapping the NRAMP1 gene were constructed, and the haplotype segregation into leprosy-affected offspring was analyzed. It was observed that the segregation of NRAMP1 haplotypes into affected siblings was significantly nonrandom. This finding is consistent with the hypothesis that NRAMP1 itself is a leprosy susceptibility locus.