title: Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen's disease) in Brazil.
abstract: Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from the state of Pará (PA). All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37-7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034) leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN) and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.
authors.affiliation: Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Sérgio Ricardo Fernandes
authors.initials: SR
authors.lastname: Araújo
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Australia.
authors.forename: Sarra Elisabeth
authors.initials: SE
authors.lastname: Jamieson
authors.affiliation: Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Kathryn Margaret
authors.initials: KM
authors.lastname: Dupnik
authors.affiliation: Instituto de Medicina Tropical do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Glória Regina
authors.initials: GR
authors.lastname: Monteiro
authors.affiliation: Instituto de Medicina Tropical do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Maurício Lisboa
authors.initials: ML
authors.lastname: Nobre
authors.affiliation: Faculdade de Medicina, Universidade do Estado do Rio Grande do Norte, Mossoró, RN, Brasil.
authors.forename: Márcia Sousa
authors.initials: MS
authors.lastname: Dias
authors.affiliation: Departamento de Clínica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Pedro Bezerra
authors.initials: PB
authors.lastname: Trindade Neto
authors.affiliation: Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Maria do Carmo Palmeira
authors.initials: Mdo C
authors.lastname: Queiroz
authors.affiliation: Instituto de Medicina Tropical do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Carlos Eduardo Maia
authors.initials: CE
authors.lastname: Gomes
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Australia.
authors.forename: Jenefer Mary
authors.initials: JM
authors.lastname: Blackwell
authors.affiliation: Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.
authors.forename: Selma Maria Bezerra
authors.initials: SM
authors.lastname: Jeronimo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000378:metabolism; D004893:Erythema Nodosum / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D015440:Leprosy, Lepromatous / Q000453:epidemiology / Q000235:genetics*; D015441:Leprosy, Tuberculoid / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012959:Socioeconomic Factors; D055815:Young Adult