RESUMO
Despite intense efforts, the number of new cases of leprosy has remained significantly high over the past 20 years. Host genetic background is strongly linked to the pathogenesis of this disease, which is caused by Mycobacterium leprae (M. leprae), and there is a consensus that the most significant genetic association with leprosy is attributed to the major histocompatibility complex (MHC). Here, we investigated the association of human leukocyte antigen (HLA) class I and II genes with leprosy in a Brazilian population encompassing 826 individuals from a hyperendemic area of Brazil; HLA typing of class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1) loci was conducted. Initially, the associations were tested using the chi-square test, with p-values adjusted using the false discovery rate (FDR) method. Next, statistically significant signals of the associations were submitted to logistic regression analyses to adjust for sex and molecular ancestry data. The results showed that HLA-C*08, -DPB1*04, and -DPB1*18 were associated with protective effects, while HLA-C*12 and -DPB1*105 were associated with susceptibility to leprosy. Thus, our findings reveal new associations between leprosy and the HLA-DPB1 locus and confirm previous associations between the HLA-C locus and leprosy.
Assuntos
Predisposição Genética para Doença , Antígenos HLA-C/genética , Cadeias beta de HLA-DP/genética , Hanseníase/genética , Adolescente , Adulto , Idoso , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Doenças Endêmicas , Feminino , Loci Gênicos , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DP/imunologia , Humanos , Hanseníase/epidemiologia , Hanseníase/imunologia , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Adulto JovemRESUMO
Host genetic susceptibility to leprosy has been intensively investigated over the last decades; however, there are no studies on the role of genetic variants in disease recurrence. A previous initiative identified three recurrent cases of leprosy for which none of the M. leprae strains, as obtained in the first and the second diagnosis, had any known genomic variants associated to resistance to Multidrug therapy; in addition, whole genome sequencing indicated that the same M. leprae was causing two out of the three recurrences. Thus, these individuals were suspected of being particularly susceptible to M. leprae infection, either as relapse or reinfection. To verify this hypothesis, 19 genetic markers distributed across 11 loci (14 genes) classically associated with leprosy were genotyped in the recurrent and in three matching non-recurrent leprosy cases. An enrichment of risk alleles was observed in the recurrent cases, suggesting the existence of a particularly high susceptibility genetic profile among leprosy patients predisposing to disease recurrence.
