Lauro de Souza Lima Institute, Bauru 17034-971, Brazil.
Lauro de Souza Lima Institute, Bauru 17034-971, Brazil; São Paulo State University (UNESP), Medical School, Botucatu 18618-687, Brazil.
Hum Immunol. 2021 Jan;82(1):11-18. doi: 10.1016/j.humimm.2020.10.008. Epub 2020 Nov 11.
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-C08, -DPB104, and -DPB118 were associated with protective effects, while HLA-C12 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.
尽管付出了巨大努力,但在过去的 20 年中,麻风病的新发病例数量仍然居高不下。宿主的遗传背景与这种疾病的发病机制密切相关,这种疾病是由麻风分枝杆菌(M. leprae)引起的,人们普遍认为与麻风病最显著的遗传关联归因于主要组织相容性复合体(MHC)。在这里,我们在一个巴西高度流行地区的 826 名个体中调查了人类白细胞抗原(HLA)I 类和 II 类基因与麻风病的关联;对 I 类(-A、-B、-C)和 II 类(-DRB1、-DQA1、-DQB1、-DPA1 和 -DPB1)基因座的 HLA 型进行了分型。最初,使用卡方检验测试关联,使用错误发现率(FDR)方法调整 p 值。接下来,对具有统计学意义的关联信号进行逻辑回归分析,以调整性别和分子祖先数据。结果表明,HLA-C08、-DPB104 和 -DPB118 与保护作用相关,而 HLA-C12 和 -DPB1*105 与麻风病易感性相关。因此,我们的研究结果揭示了麻风病与 HLA-DPB1 基因座之间的新关联,并证实了 HLA-C 基因座与麻风病之间的先前关联。