Ahmed A R, Foster S, Zaltas M, Notani G, Awdeh Z, Alper C A, Yunis E J
Department of Oral Pathology, Harvard School of Dental Medicine, Boston, MA.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11579-82. doi: 10.1073/pnas.88.24.11579.
Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and II and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB10301). The frequency of DQB10301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P less than 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB10301 among the patients was consistent with dominant but not recessive inheritance of DQB10301 or a gene, probably a class II allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP.
眼瘢痕性类天疱疮（OCP）是一种自身免疫性水疱病，可累及结膜和多处黏膜。对20名白种人OCP患者及其家庭成员的主要组织相容性复合体的Ⅰ类、Ⅱ类和补体遗传标记进行了研究。将患者个体等位基因以及常见的固定或扩展单倍型的频率与正常家族对照单倍型以及总体正常白种人单倍型的频率进行了比较。与总体对照相比，最显著增加的是HLA-DQw3（P = 0.006），它与任何扩展单倍型均无关联。20名患者中除1名外，其余所有患者携带的DQw3均与HLA-DR4（与总体正常基因型对照相比显著增加，P = 0.042）或DR5连锁。通过基因组DNA的限制性片段长度多态性分析，每次检测到的DQw3均为DQw7（3.1，DQB10301）。与总体正常的携带DR4和DR5 DQw3的单倍型相比，患者单倍型中DQB10301的频率在统计学上显著增加（P小于0.003，相对风险 = 9.6）。患者中DQB10301纯合子和杂合子的分布与DQB10301或与其处于连锁不平衡状态的一个基因（可能是一个Ⅱ类等位基因）作为OCP主要组织相容性复合体易感基因的显性而非隐性遗传一致。
