Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India.

Journal article

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.

Authors: Tosh, K; Ravikumar, M; Bell, J; Meisner, S; Hill, A

• Publication status: Published
• Journal: Human molecular genetics
• Volume: 15
• Issue: 19
• Pages: 2880-2887
• Publication date: 2006-10-01
• DOI: 10.1093/hmg/ddl229
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Base Sequence; India; Alleles; Haplotypes; Microsatellite Repeats; DNA Primers; Linkage Disequilibrium; Female; Genetic Variation; Genes, MHC Class I; Leprosy; Histocompatibility Antigens Class I; Humans; Polymorphism, Genetic; Male