Ollier W, Silman A, Gosnell N, Currey H, Awad J, Doyle P, McCloskey D, Alonso A, Hossain M A, Festenstein H
Department of Immunology, London Hospital Medical College.
Dis Markers. 1986 Jun;4(1-2):85-98.
In a study of multicase RA families, significantly raised frequencies of the HLA antigens DR4, DR1, Bw62, Cw3, A2, A31 and significantly lower frequencies of DR2, DR3, and B8 were found in probands compared to normal controls. When haplotype frequencies were compared between probands and controls, two haplotypes A2-B44-DR4 and A2-Bw62-DR4 were at higher frequency in probands. These differences no longer reached significance when only DR4-containing haplotypes were compared between probands and controls. A significantly lower haplotype frequency of A1-B8-DR3 was observed in probands compared to controls. This difference did not remain significant when only non-DR4 haplotypes were compared. Using an affected sibling pair ratio method, significant linkage between HLA and RA was found (P less than 0.01). Significant linkage was also observed between HLA and seropositivity. Analysis of Hardy-Weinberg equilibrium for the DR locus did not support the suggestion that DR4-associated RA susceptibility was inherited as a dominant trait. In addition it did not support the notion of an additive effect of DR4 and DR1 in RA susceptibility as these antigens were not found together more frequently than predicted by their individual gene frequencies.
在一项针对多病例类风湿关节炎（RA）家族的研究中，与正常对照组相比，先证者中HLA抗原DR4、DR1、Bw62、Cw3、A2、A31的频率显著升高，而DR2、DR3和B8的频率显著降低。当先证者与对照组之间比较单倍型频率时，两种单倍型A2 - B44 - DR4和A2 - Bw62 - DR4在先证者中的频率较高。当先证者与对照组之间仅比较含DR4的单倍型时，这些差异不再具有统计学意义。与对照组相比，先证者中观察到A1 - B8 - DR3单倍型频率显著降低。当仅比较非DR4单倍型时，这种差异不再具有统计学意义。使用患病同胞对比例法，发现HLA与RA之间存在显著连锁（P小于0.01）。在HLA与血清阳性之间也观察到显著连锁。对DR基因座的哈迪-温伯格平衡分析不支持DR4相关的RA易感性作为显性性状遗传的观点。此外，它也不支持DR4和DR1在RA易感性中具有累加效应的观点，因为这些抗原同时出现的频率并不比根据其各自基因频率预测的频率更高。
