ABSTRACT
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.
Subject(s)
Genetic Predisposition to Disease , HLA-C Antigens/genetics , HLA-DP beta-Chains/genetics , Leprosy/genetics , Adolescent , Adult , Aged , Alleles , Brazil/epidemiology , Case-Control Studies , Endemic Diseases , Female , Genetic Loci , HLA-C Antigens/immunology , HLA-DP beta-Chains/immunology , Humans , Leprosy/epidemiology , Leprosy/immunology , Leprosy/microbiology , Male , Middle Aged , Mycobacterium leprae/immunology , Young AdultABSTRACT
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(AU).
Subject(s)
Genetic Predisposition to Disease , Leprosy/genetics , Mycobacterium leprae/pathogenicity , HLA-C Antigens , Alleles , Major Histocompatibility ComplexABSTRACT
Os Herpesvírus humano 1-8 infectam hospedeiros específicos e são indicativos de alto nível adaptativo causando patogenicidade significativa apenas em situações de desequilíbrio fisiológico do hospedeiro. O Mycobacterium leprae (M. leprae) é o agente etiológico da hanseníase que causa deformidade e lesões de pele. Em 2008, foi identificada uma nova espécie de micobactéria denominada Mycobacterium lepromatosis (M. lepromatosis) que foi inicialmente associada a Hanseníase Lepromatosa Difusa. Considerando a hipótese evolutiva de interação endossimbiótica entre seres celulares e acelulares, que os herpesvírus e o gênero Mycobacterium podem ter se originado próximo e/ou dentro da Era Mesozoica, são parasitas intracelulares e possuem tropismo celular em comum, foi realizada uma comparação filogenética do M. leprae e M. lepromatosis com os herpesvírus humano 1-8 utilizando os softwares BLAST e MEGA7 visando encontrar ou não evidencias de interação entre esses micro-organismos. Como resultado foi evidenciado similaridade genética entre o M. leprae e os Alphaherpesvírus humano 1-3. Portanto inferimos uma possível relação evolutiva entre o M. leprae com esses herpesvírus.
