CUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam View Full Text


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Article Info

DATE

2014-02-23

AUTHORS

Audrey V. Grant, Aurelie Cobat, Nguyen Van Thuc, Marianna Orlova, Nguyen Thu Huong, Jean Gaschignard, Andrea Alter, Nguyen Ngoc Ba, Vu Hong Thai, Laurent Abel, Alexandre Alcaïs, Erwin Schurr

ABSTRACT

Leprosy is caused by infection with Mycobacterium leprae and is classified clinically into paucibacillary (PB) or multibacillary (MB) subtypes based on the number of skin lesions and the bacillary index detected in skin smears. We previously identified a major PB susceptibility locus on chromosome region 10p13 in Vietnamese families by linkage analysis. In the current study, we conducted high-density association mapping of the 9.5 Mb linkage peak on chromosome region 10p13 covering 39 genes. Using leprosy per se and leprosy subtypes as phenotypes, we employed 294 nuclear families (303 leprosy cases, 63 % MB, 37 % PB) as a discovery sample and 192 nuclear families (192 cases, 55 % MB, 45 % PB) as a replication sample. Replicated significant association signals were revealed in the genes for cubilin (CUBN) and nebulette (NEBL). In the combined sample, the C allele (frequency 0.26) at CUBN SNP rs10904831 showed association [p = 1 × 10−5; OR 0.52 (0.38–0.7)] with MB leprosy only. Likewise, allele T (frequency 0.42) at NEBL SNP rs11012461 showed association [p = 4.2 × 10−5; OR 2.51 (1.6–4)] with MB leprosy only. These associations remained valid for the CUBN signal when taking into account the effective number of tests performed (type I error significance threshold = 2.4 × 10−5). We used the results of our analyses to propose a new model for the genetic control of polarization of clinical leprosy. More... »

PAGES

883-893

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-014-1430-8

    DOI

    http://dx.doi.org/10.1007/s00439-014-1430-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022255196

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24563210


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