Vanderborght P R, Pacheco A G, Moraes M E, Antoni G, Romero M, Verville A, Thai V H, Huong N T, Ba N N, Schurr E, Sarno E N, Moraes M O
Leprosy Laboratory, Department of Mycobacterioses, Oswaldo Cruz Institute, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro 21045-900, RJ, Brazil.
Genes Immun. 2007 Jun;8(4):320-4. doi: 10.1038/sj.gene.6364390. Epub 2007 Mar 29.
The host genetic background has been considered one of the factors that influence leprosy outcome, a chronic infectious disease caused by Mycobacterium leprae. Genome scans demonstrated that the 6p21 region is associated with leprosy and a substantial number of population-based studies analyzing human leukocyte antigen (HLA) class II loci suggested association of HLA-DR with leprosy. However, some studies lacked robustness as they had limited power. Indeed, experimental designs require increased sample size to achieve adequate power, as well as replication studies with independent samples for confirmation of previous findings. In this work, we analyzed the influence of the HLA-DRB1 locus on leprosy susceptibility per se and disease type using a case-control design carried out in Brazilians (578 cases and 691 controls) and a replication study based on a family design in a Vietnamese population (n=194 families). The results showed that HLA-DRB110 is associated with susceptibility to leprosy and HLA-DRB104 is associated with resistance, both in the Brazilian and Vietnamese populations suggesting that these alleles play an important role in the activation of cellular immune responses against M. leprae.
宿主遗传背景被认为是影响麻风病(一种由麻风分枝杆菌引起的慢性传染病)预后的因素之一。基因组扫描表明,6p21区域与麻风病相关,大量基于人群的分析人类白细胞抗原(HLA)II类基因座的研究表明HLA-DR与麻风病有关。然而,一些研究由于效力有限而缺乏稳健性。实际上,实验设计需要增加样本量以获得足够的效力,以及使用独立样本进行重复研究以证实先前的发现。在这项研究中,我们采用病例对照设计(在巴西人样本中包括578例病例和691例对照),并基于越南人群的家系设计进行重复研究(n = 194个家系),分析了HLA-DRB1基因座对麻风病易感性本身及疾病类型的影响。结果表明,在巴西人和越南人群中,HLA-DRB110与麻风病易感性相关,而HLA-DRB104与抗性相关,这表明这些等位基因在激活针对麻风分枝杆菌的细胞免疫反应中起重要作用。