The complex pattern of genetic associations of leprosy with HLA class I and class II alleles can be reduced to four amino acid positions.
PLoS Pathog
; 16(8): e1008818, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32776973
ABSTRACT
Leprosy is a chronic disease caused by Mycobacterium leprae. Worldwide, more than 200,000 new patients are affected by leprosy annually, making it the second most common mycobacterial disease after tuberculosis. The MHC/HLA region has been consistently identified as carrying major leprosy susceptibility variants in different populations at times with inconsistent results. To establish the unambiguous molecular identity of classical HLA class I and class II leprosy susceptibility factors, we applied next-generation sequencing to genotype with high-resolution 11 HLA class I and class II genes in 1,155 individuals from a Vietnamese leprosy case-control sample. HLA alleles belonging to an extended haplotype from HLA-A to HLA-DPB1 were associated with risk to leprosy. This susceptibility signal could be reduced to the HLA-DRB1*1001~ HLA-DQA1*0105 alleles which were in complete linkage disequilibrium (LD). In addition, haplotypes containing HLA-DRB3~ HLA-DRB1*1202 and HLA-C*0706~ HLA-B*4403~ HLA-DRB1*0701 alleles were found as two independent protective factors for leprosy. Moreover, we replicated the previously associated HLA-DRB1*1501 as leprosy risk factor and HLA-DRB1*0405~HLA-DQA1*0303 as protective alleles. When we narrowed the analysis to the single amino acid level, we found that the associations of the HLA alleles were largely captured by four independent amino acids at HLA-DRß1 positions 57 (D) and 13 (F), HLA-B position 63 (E) and HLA-A position 19 (K). Hence, analyses at the amino acid level circumvented the ambiguity caused by strong LD of leprosy susceptibility HLA alleles and identified four distinct leprosy susceptibility factors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Classe I
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Antígenos de Histocompatibilidade Classe II
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Predisposição Genética para Doença
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Aminoácidos
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Hanseníase
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Mutação
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article