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Human Molecular Genetics Advance Access originally published online on August 21, 2006
Human Molecular Genetics 2006 15(19):2880-2887; doi:10.1093/hmg/ddl229
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Kerrie Tosh1,{dagger},{ddagger}, Muthuswamy Ravikumar2,{dagger},{ddagger}, Jordana Tzenova Bell1, Sarah Meisner1,{ddagger}, Adrian V.S. Hill1,* and Ramasamy Pitchappan2

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

* To whom correspondence should be addressed. Tel: +44 1865287759; Fax: +44 1865287686; Email: adrian.hill{at}well.ox.ac.uk

Received May 24, 2006; Accepted August 10, 2006

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}ß 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.

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be considered as joint First Authors.

{ddagger} Present Addresses: Kerrie Tosh, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK; Muthuswamy Ravikumar, Department of Pathology, 323A, Health Science Research Facility, 89 Beaumont Avenue, Burlington, Vermont-05405, USA; Sarah Meisner, Bath Royal United Hospital Trust, Combe Park, Bath BA1 3NG, UK.


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