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
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India
,
,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 
T cells, CD8+ 
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.
The authors wish it to be known that, in their opinion, the first two authors should be considered as joint First Authors.
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. M. Blackwell, S. E. Jamieson, and D. Burgner HLA and Infectious Diseases Clin. Microbiol. Rev., April 1, 2009; 22(2): 370 - 385. [Abstract] [Full Text] [PDF]
|
|