Reveille J D, Suarez Almazor M E, Russell A S, Go R C, Appleyard J, Barger B O, Acton R T, Koopman W J, McDaniel D O
Department of Medicine, University of Texas Health Science Center at Houston 77225.
Semin Arthritis Rheum. 1994 Apr;23(5):295-309. doi: 10.1016/0049-0172(94)90026-4.
Linkage analysis of HLA haplotypes, HLA-B27 subtypes, and a 9.2-kb PvuII B7 restriction fragment length polymorphism (RFLP) (shown previously to be associated with peripheral arthritis in ankylosing spondylitis [AS]) in 115 relatives from 12 multiplex spondyloarthropathy (SNSA) and 2 B27-positive control families showed AS to be linked to HLA-B27 haplotypes. The RFLP segregated with HLA-A3- and HLA-A9-bearing haplotypes (lod score, 10.98; odds in favor of linkage, 9.2 x 10(10):1), although its linkage to AS or other SNSA per se was not seen. The association of HLA-A3/A9 with the RFLP was also seen in 52 AS patients and 92 controls, although no HLA-A, -B, -C, or -DR allele (other than HLA-B27) was significantly increased in frequency. The HLA-B27 subtype seen on all but one of the haplotypes studied was B2705, the sole exception being HLA-B2702. Although not ruling out a second HLA-A-linked gene influencing the clinical expression of AS, these data fail to support the role of a second MHC-associated gene in the pathogenesis of AS per se.
对来自12个多发性脊柱关节病（SNSA）家庭和2个B27阳性对照家庭的115名亲属进行了HLA单倍型、HLA - B27亚型以及一个9.2kb PvuII B7限制性片段长度多态性（RFLP）（先前已证明与强直性脊柱炎[AS]的外周关节炎相关）的连锁分析，结果显示AS与HLA - B27单倍型连锁。该RFLP与携带HLA - A3和HLA - A9的单倍型共分离（对数优势分数为10.98；连锁优势比为9.2×10(10):1），尽管未发现其与AS或其他SNSA本身存在连锁关系。在52例AS患者和92例对照中也观察到HLA - A3/A9与RFLP的关联，尽管除HLA - B27外，HLA - A、-B、-C或 - DR等位基因的频率均未显著增加。在所研究的除一个单倍型外的所有单倍型上观察到的HLA - B27亚型均为B2705，唯一例外是HLA - B2702。尽管不能排除第二个与HLA - A连锁的基因影响AS的临床表型，但这些数据不支持第二个MHC相关基因在AS发病机制中的作用。
