02123nas a2200277   4500000000100000008004100001260001600042653001200058653002000070653001200090100001200102700001200114700001500126700001300141700001300154700001800167700001200185700001000197700001200207700001100219700001400230700001300244245012800257520144600385022001401831       2014                            d  c2014 Feb 2310aleprosy10aGenetic factors10aVietnam1 aGrant A1 aCobat A1 aVan Thuc N1 aOrlova M1 aHuong NT1 aGaschignard J1 aAlter A1 aBa NN1 aThai VH1 aAbel L1 aAlcaïs A1 aSchurr E00aCUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam.3 aLeprosy 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.  a1432-1203