Rich S S, Weitkamp L R, Barbosa J
Am J Hum Genet. 1984 Sep;36(5):1015-23.
Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.
对200名胰岛素依赖型（I型）糖尿病（IDDM）患者进行了HLA - B、HLA - DR和备解素因子B（Bf）分型。将患者的HLA和Bf抗原及单倍型频率与第8届HLA研讨会得出的对照频率进行了比较。还将扩展单倍型（由染色体上的B - Bf - DR等位基因定义）的频率与对照频率进行了对比。证实了IDDM与HLA - B8、DR3、DR4、BfS和BfF1之间存在显著的正相关，以及IDDM与HLA - B7、DR2、DR5、DR7和BfF之间存在显著的负相关。一种单倍型（B7 - BfS - DR2）表现出显著的负相关，而五种单倍型（B8 - BfS - DR3、B8 - BfS - DR4、B15 - BfS - DR4、B18 - BfF1 - DR3和B40 - BfS - DR4）与IDDM表现出显著的正相关。在这个样本中，所有先证者中有64%携带至少一种高风险单倍型。总之，与IDDM相关的五种“高风险”单倍型的出现为之前未记录的遗传异质性提供了证据，并表明可能有超过两个HLA区域基因参与IDDM易感性。
