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.
BT - Human molecular genetics C1 - http://www.ncbi.nlm.nih.gov/pubmed/16923796?dopt=Abstract CN - TOSH 2006 DA - 2006 Oct 01 DO - 10.1093/hmg/ddl229 IS - 19 J2 - Hum. Mol. Genet. LA - eng N2 -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.
PY - 2006 SP - 2880 EP - 7 T2 - Human molecular genetics TI - Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. UR - http://hmg.oxfordjournals.org/content/15/19/2880.full.pdf+html?sid=de3dbd9d-0ff5-4cf6-98cd-b9bfdc8cfdca VL - 15 SN - 0964-6906 ER -