Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India.
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.
Tosh
Kerrie
K
The Wellcome Trust Centre for Human Genetics, Oxford, UK.
Ravikumar
Muthuswamy
M
Bell
Jordana Tzenova
JT
Meisner
Sarah
S
Hill
Adrian V S
AV
Pitchappan
Ramasamy
R
D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005805:Genes, MHC Class I; D014644:Genetic Variation; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D007918:Leprosy / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen