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巴西南部肾移植候选者中 MICA 多样性与 HLA-B 等位基因的连锁不平衡。

MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant candidates in southern Brazil.

机构信息

Department of Basic Health Science, Universidade Estadual de Maringá - Maringá, Paraná, Brazil.

Laboratório de Imunogenética e Histocompatibilidade, Department of Genetics, Universidade Federal do Paraná - Curitiba, Paraná, Brazil.

出版信息

PLoS One. 2017 Apr 18;12(4):e0176072. doi: 10.1371/journal.pone.0176072. eCollection 2017.

Abstract

The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA008 (21.6%), MICA002 (17.0%) and MICA004 (14.8%). The most common haplotypes were MICA009-B51 (7.8%), MICA004-B44 (6.06%) and MICA002-B35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

摘要

主要组织相容性复合体(MHC)I 类链相关基因 A(MICA)位于人类白细胞抗原(HLA)-B 的着丝粒侧。这些 MHC 基因座之间的短距离表明存在连锁不平衡(LD)。与 HLA 类似,MICA 高度多态性,不同人群中这种多态性尚未得到很好的记录。在这项研究中,我们估计了巴西南部 346 名肾移植候选者中 MICA 的等位基因频率和与 HLA-B 等位基因的连锁不平衡。使用聚合酶链反应-序列特异性引物方法(PCR-SSO)结合 Luminex 技术对 MICA 和 HLA 进行分型。共鉴定出 19 个 MICA 等位基因群。最常见的等位基因群是 MICA008(21.6%)、MICA002(17.0%)和 MICA004(14.8%)。最常见的单倍型是 MICA009-B51(7.8%)、MICA004-B44(6.06%)和 MICA002-B35(5.63%)。由于 MICA 和 HLA-B 基因座的接近,大多数单倍型显示出强烈的 LD。来自巴西同一地区的肾患者和健康受试者在 MICA 多态性方面存在统计学显著差异。MICA027 等位基因组在肾患者中更为常见(Pc=0.018,OR:3.421,95%CI:1.516-7.722),而 MICA*019 等位基因组在健康受试者中更为常见(Pc=0.001,OR:0.027,95%CI:0.002-0.469)。本研究提供了巴西肾移植候选者中 MICA 多态性分布及其与 HLA-B 等位基因连锁不平衡的信息。这些信息应有助于确定慢性肾病患者易患不同疾病的机制,并阐明与 MICA 多态性相关的同种异体移植排斥的机制。

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