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In a study of mainly paucibacillary leprosy-affected sib-pair families from South India, in addition to the expected associations with the HLA-DRB1 locus, we have identified significant association with a functional variant of the MICA gene as well as a microsatellite in the flanking region of the MICB gene. The associations with MICA and MICB cannot be accounted for by linkage disequilibrium with the HLA class II locus indicating a role in genetic susceptibility to leprosy that is independent of HLA-DRB1. Previous studies have shown that MICA and MICB are expressed on the surface of cells in response to infection, where they are recognized by the NKG2D receptor on gammadelta T cells, CD8+ alphabeta T cells and natural killer cells, all of which contribute to defense against mycobacteria. The MICA*5A5.1 allele, associated here with leprosy susceptibility, encodes a protein lacking a cytoplasmic tail providing a possible mechanism for defective immune surveillance against mycobacteria.

Original publication

DOI

10.1093/hmg/ddl229

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/10/2006

Volume

15

Pages

2880 - 2887

Keywords

Alleles, Base Sequence, DNA Primers, Female, Genes, MHC Class I, Genetic Variation, Haplotypes, Histocompatibility Antigens Class I, Humans, India, Leprosy, Linkage Disequilibrium, Male, Microsatellite Repeats, Polymorphism, Genetic