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.

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

“…Upon invasion, M. leprae stimulates ERBB2 independently of ERBB3 ( 82 ), resulting in ERK1/2 activation, which leads to peripheral nerves demyelination ( 83 ). ERBB2 miRNAs were downregulated in LL patients (Figure 9 ), indicating a possible role for the SOX2 and JUN pathway in demyelination and EMT ( 78 ).…”

The role of ERBB2 gene polymorphisms in leprosy susceptibility

“…The data showed here support previous observations of a lack of association between ERBB2 genetic variants and susceptibility to leprosy per se in a similar population-based case-control data set from Rio Grande do Norte. 6 Our population-based study in Bahia and that in Rio Grande do Norte had larger sample sizes than the smaller family-based study in Pará, suggesting that the association observed in the latter population may represent a false positive result. However, Araújo et al 6 draw attention to the fact that ERBB2 lies under a linkage peak 8 , 9 for leprosy observed in the same large pedigrees employed for the study in Pará State.…”

“… 6 Our population-based study in Bahia and that in Rio Grande do Norte had larger sample sizes than the smaller family-based study in Pará, suggesting that the association observed in the latter population may represent a false positive result. However, Araújo et al 6 draw attention to the fact that ERBB2 lies under a linkage peak 8 , 9 for leprosy observed in the same large pedigrees employed for the study in Pará State. The region of the linkage peak at chromosome 17q11-q22 is a gene dense region of potential immunological candidate genes contributing to leprosy susceptibility.…”

“…Recent data have shown that polymorphisms in the ERBB2 gene were associated with leprosy development in families from Pará State, but not in a population from the state of Rio Grande do Norte in Brazil. 6 Herein we investigate a geographically distinct population from Northeastern Brazil to further evaluate the role of this gene in leprosy susceptibility. The state of Bahia is considered of medium endemicity, according to the parameter of prevalence.…”

Estado da arte na hanseníase: Revisão integrativa em três periódicos brasileiros de impacto internacional

“…Neste contexto, estudos buscam a presença de genes que apontem susceptibilidade a hanseníase em localidades endêmicas 19,28 , bem como de biomarcadores em tatus selvagens 35 , porém sem fortes evidências. Diferentes pesquisas têm investigado antígenos através de sorologia e biomarcadores para hanseníase, na perspectiva de melhorar a sensibilidade de testes laboratoriais para identificação precoce da doença.…”