Original Investigation

Human Genetics

, Volume 133, Issue 7, pp 883-893

First online:

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

  • Audrey V. GrantAffiliated withLaboratoire de Génétique Humaine des Maladies Infectieuses, Branche Necker, Institut National de la Santé et de la Recherche Médicale, U980Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine
  • , Aurelie CobatAffiliated withMcGill International TB Centre, The Research Institute of the McGill University Health CentreDepartments of Medicine and Human Genetics, McGill University
  • , Nguyen Van ThucAffiliated withHospital for Dermato-Venerology
  • , Marianna OrlovaAffiliated withMcGill International TB Centre, The Research Institute of the McGill University Health Centre
  • , Nguyen Thu HuongAffiliated withHospital for Dermato-Venerology
  • , Jean GaschignardAffiliated withLaboratoire de Génétique Humaine des Maladies Infectieuses, Branche Necker, Institut National de la Santé et de la Recherche Médicale, U980Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine
  • , Andrea AlterAffiliated withMcGill International TB Centre, The Research Institute of the McGill University Health CentreDepartments of Medicine and Human Genetics, McGill University
  • , Nguyen Ngoc BaAffiliated withHospital for Dermato-Venerology
  • , Vu Hong ThaiAffiliated withHospital for Dermato-Venerology
    • , Laurent AbelAffiliated withLaboratoire de Génétique Humaine des Maladies Infectieuses, Branche Necker, Institut National de la Santé et de la Recherche Médicale, U980Université Paris Descartes, Sorbonne Paris Cité, Institut ImagineSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University
    • , Alexandre AlcaïsAffiliated withLaboratoire de Génétique Humaine des Maladies Infectieuses, Branche Necker, Institut National de la Santé et de la Recherche Médicale, U980Université Paris Descartes, Sorbonne Paris Cité, Institut ImagineURC, CIC, Necker, and Cochin Hospitals
    • , Erwin SchurrAffiliated withMcGill International TB Centre, The Research Institute of the McGill University Health CentreDepartments of Medicine and Human Genetics, McGill UniversityMontreal General Hospital Research Institute Email author 

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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.