Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis.

P Spagnolo, H Sato, J C Grutters, E A Renzoni, S E Marshall, H J T Ruven, A U Wells, A Tzouvelekis, C H M van Moorsel, J M M van den Bosch, R M du Bois, K I Welsh
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引用次数: 79

Abstract

Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren's syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA-DRB1 alleles, by sequence-specific primers-polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA-DRB1*14 [odds ratio (OR) = 3.1, P(c) = 0.0003], DRB1*12 (OR = 2.5, P(c) = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, P(c) = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren's syndrome and after adjusting for HLA-DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Löfgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4--but not rs2076530 A--are associated with non-Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed.

英国和荷兰结节病患者BTNL2基因多态性分析。
结节病是一种异质性疾病,在表型和遗传上都是如此。最近的两项独立研究表明,嗜丁酸蛋白样2 (BTNL2)基因的功能多态性与人类白细胞抗原(HLA)-DRB1等位基因无关,易患结节病。然而,在这两项研究中,数据分析没有按Löfgren综合征(临床和遗传上不同的结节病亚群)分层。BTNL2可能编码一种免疫辅助受体,与HLA-DRB1相邻且处于连锁不平衡(LD)状态。我们通过序列特异性引物-聚合酶链反应研究了来自两个欧洲国家的288例患者和446例对照者的6个BTNL2变异,包括功能性rs2076530 (G > A)和HLA-DRB1等位基因。在整个患者组中,HLA-DRB1*14[比值比(OR) = 3.1, P(c) = 0.0003]、DRB1*12 (OR = 2.5, P(c) = 0.003)、BTNL2 rs2076530a等位基因(OR = 1.49, P(c) = 0.002)均与疾病易感性相关。然而,在排除Löfgren综合征患者并调整HLA-DRB1等位基因后,BTNL2 rs2076530a与疾病的相关性消失(P = 0.23)。相比之下,HLA-DRB1*14和DRB1*12均保持强显著性(OR = 3.60, P < 0.0001和OR = 3.03, P = 0.003)。在调整HLA-DRB1等位基因后,rs2076530g等位基因标记的BTNL2单倍型4也与non-Löfgren结节病相关(OR 0.37, P = 0.016)。总之,HLA-DRB1*14, DRB1*12和BTNL2单倍型4-但不包括rs2076530a -与non-Löfgren结节病相关。然而,整个HLA复合体的紧密LD使得难以确定易感位点/i的精确位置。来自不同种族群体的更大的样本集,更精细的绘图,以及在HLA区域更可靠的LD分析是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue antigens
Tissue antigens 医学-病理学
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