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Human Molecular Genetics Advance Access published online on August 21, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl229
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received May 24, 2006
Revised August 10, 2006
Accepted August 10, 2006

Article

Variation In MICA And MICB Genes And Enhanced Susceptibility To Paucibacillary Leprosy In South India

Kerrie Tosh 1, Muthuswamy Ravikumar 2, Jordana Tzenova Bell 1, Sarah Meisner 1, Adrian V.S. Hill 1 *, and Ramasamy Pitchappan 2

1 The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK
2 Centre for Excellence in Genomic Sciences, Madurai Kamaraj University, Madurai 625021, India

* To whom correspondence should be addressed.
Adrian V.S. Hill, E-mail: adrian.hill{at}well.ox.ac.uk


  Abstract

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 {gamma}{delta} T cells, CD8+ {alpha}{beta} T cells and NK 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.


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