02796nas a2200469   4500000000100000008004100001260001300042653002500055653002000080653002300100653001000123653003800133653001100171653002000182653001200202653002700214653002800241653002000269653002400289653002500313653003600338653002000374653002800394653001700422100001200439700001700451700001500468700001200483700001300495700001000508700001400518700001300532700001100545700001300556700001400569700001300583245009900596300001100695490000800706520159800714022001402312       2010                            d  c2010 Mar10aCase-Control Studies10aCells, Cultured10aCloning, Molecular10aExons10aGenetic Predisposition to Disease10aHumans10aLectins, C-Type10aleprosy10aLinkage Disequilibrium10aMannose-Binding Lectins10aMutant Proteins10aMycobacterium bovis10aMycobacterium leprae10aPolymorphism, Single Nucleotide10aProtein Binding10aReceptors, Cell Surface10aTransfection1 aAlter A1 aLéséleuc L1 aVan Thuc N1 aThai VH1 aHuong NT1 aBa NN1 aCardoso C1 aGrant AV1 aAbel L1 aMoraes M1 aAlcaïs A1 aSchurr E00aGenetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility.  a337-480 v1273 a<p>The chromosomal region 10p13 has been linked to paucibacillary leprosy in two independent studies. The MRC1 gene, encoding the human mannose receptor (MR), is located in the 10p13 region and non-synonymous SNPs in exon 7 of the gene have been suggested as leprosy susceptibility factors. We determined that G396S is the only non-synonymous exon 7-encoded polymorphism in 396 unrelated Vietnamese subjects. This SNP was genotyped in 490 simplex and 90 multiplex leprosy families comprising 704 patients (47% paucibacillary; 53% multibacillary). We observed significant under-transmission of the serine allele of the G396S polymorphism with leprosy per se (P = 0.036) and multibacillary leprosy (P = 0.034). In a sample of 384 Brazilian leprosy cases (51% paucibacillary; 49% multibacillary) and 399 healthy controls, we observed significant association of the glycine allele of the G396S polymorphism with leprosy per se (P = 0.016) and multibacillary leprosy (P = 0.023). In addition, we observed a significant association of exon 7 encoded amino acid haplotypes with leprosy per se (P = 0.012) and multibacillary leprosy (P = 0.004). Next, we tested HEK293 cells over-expressing MR constructs (293-MR) with three exon 7 haplotypes of MRC1 for their ability to bind and internalize ovalbumin and zymosan, two classical MR ligands. No difference in uptake was measured between the variants. In addition, 293-MR failed to bind and internalize viable Mycobacterium leprae and BCG. We propose that the MR-M. leprae interaction is modulated by an accessory host molecule of unknown identity.</p>  a1432-1203