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Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen's disease) in Brazil

This study examines whether polymorphisms in the ERBB2 gene were associated with leprosy in primary and replication cohorts from northeastern Brazil.

Authors:
Araújo SRF,Jamieson SE, Dupnik KM, Monteiro GR, Nobre ML, Dias MS, Neto PBT, Queiroz MCP, Gomes CEM, Blackwell JM, Jeronimo SMB

Authors notes:
Memorias do Instituto Oswaldo Cruz 109(2): 182-188

Keywords:
Brazil, ErbB2 receptor, Genetic susceptibility, Leprosy

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.

Lepromatous (LL) and tuberculoid (TT) 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.