Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-04

AUTHORS

Alexandre Alcaïs, Andrea Alter, Guillemette Antoni, Marianna Orlova, Nguyen Van Thuc, Meenakshi Singh, Patrícia R Vanderborght, Kiran Katoch, Marcelo T Mira, Vu Hong Thai, Ngyuen Thu Huong, Nguyen Ngoc Ba, Milton Moraes, Narinder Mehra, Erwin Schurr, Laurent Abel

ABSTRACT

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases. More... »

PAGES

517-522

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng2000

DOI

http://dx.doi.org/10.1038/ng2000

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039254557

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17353895


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