Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen’s disease) in Brazil.
Leprosy; genetic susceptibility; ErbB2 receptor; Brazil.
Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, mediating Mycobacterium leprae-induced demyelination. ERBB2 lies within a leprosy susceptibility locus on Chromosome 17q11-q21. To determine whether polymorphisms at ERBB2 contribute to this linkage peak, 3 haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from Pará State. All 3 tag-SNPs associated (best SNP rs2517959 OR=2.22; 95%CI 1.37-3.59; P=0.001) with leprosy per se. Lepromatous (OR=3.25; 95%CI 1.37-7.70; P=0.007) and tuberculoid (OR=1.79; 95%CI 1.04-3.05; P=0.034) leprosy both contributed to the association, consistent with previous linkage to chromosome 17q11-q21 in this study population and supporting the functional role of ERBB2 in disease pathogenesis per se. To try to replicate these findings, 6 SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 cases and 370 controls from Rio Grande do Norte (RN), and data analyzed using logistic regression analysis. None of the associations were replicated for the RN sample, whether analyzed for leprosy per se, lepromatous, tuberculoid, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains equivocal.