Behçet disease is a multi‐system disease associated with human leukocyte antigen (HLA) class I polymorphism. High‐resolution next‐generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic‐matched controls were genotyped for HLA class I loci (HLA‐A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High‐resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA‐B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5–79; P < 0·0001], HLA‐B*15:03 (OR = 12·15, 95% CI = 3·7–50·7; P < 0·0001), HLA‐C*16:02 (OR = 6·53, 95% CI = 3–14; P < 0·0001), HLA‐A*68:02 (OR = 3·14, 95% CI = 1·1–8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA‐DRB1*13:01 and HLA‐DQB1*06:03 (OR = 3·39, 95% CI = 0·9–18·9; P = 0·04 for both). By contrast, HLA‐A*03:01 (OR = 0·13, 95% CI = 0–0·8; P = 0·01) and HLA‐DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06–1·03; P = 0·02). We identified strong linkage disequilibrium between HLA‐B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA‐B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06–8·3; P = 0·01). In Egyptian Behçet patients, HLA‐B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

中文翻译：

---

白塞病，疾病关联和表现的新见解：下一代测序研究

白塞病是一种与人类白细胞抗原（HLA）I类多态性相关的多系统疾病。以前没有针对这种疾病进行过具有单倍型分析的高分辨率下一代测序 (NGS)。根据国际研究组 (ISG) 白塞病标准诊断的 60 名埃及患者和 160 名健康地理和种族匹配的对照者进行了 HLA I 类基因座 (HLA-A、B、C) 的基因分型。对于 HLA II 类基因座（DRB1、DRB3/4/5、DQA1、DQB1、DPA1、DPB1），对 40 个对照样本进行了基因分型。使用 NGS 进行高分辨率 HLA 基因分型并分析结果。临床表现为口腔溃疡 (100%)、生殖器溃疡 (100%)、眼 (55%) 和神经系统 (28%) 和血管受累 (35%)。HLA-B*51:08 [优势比 (OR) = 19·75, 95% 置信区间 (CI) = 6·5–79;P  < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7–50·7; P  < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P  < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P  < 0·01 ) 被发现与白塞病有关，HLA-DRB1*13:01 和 HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9–18·9; P  = 0· 04 两者都适用）。相比之下，HLA-A*03:01 (OR = 0·13, 95% CI = 0–0·8; P  = 0·01) 和 HLA-DPB1*17:01 被发现具有保护性 (OR = 0 ·27, 95% CI = 0·06–1·03; P = 0·02)。我们在与白塞病相关的单倍型中发现了 HLA-B*51:08 和 C*16:02 和 A*02:01 之间的强连锁不平衡。HLA-B*51:08 与法定失明显着相关（OR = 2·98，95% CI = 1·06–8·3；P  = 0·01）。在埃及 Behçet 患者中，HLA-B*51:08 是最常见的易感等位基因，对眼睛受累的预后较差。