Serjeantson S, Kirk R L, Dry P J, Ryan D P, Court J, Zimmet P, Stepanas A V
Med J Aust. 1980 Feb 9;1(3):107-9. doi: 10.5694/j.1326-5377.1980.tb134679.x.
The pathogenesis of insulin-dependent diabetes mellitus (IDDM) will remain obscure until the number of genetic mechanisms contributing to susceptibility can be clarified. Australian multiple-case families of IDDM have been examined for concordance in IDDM and HLA haplotypes and analysed for goodness-of-fit to hypotheses of one or two high-risk susceptibility genes. Diabetic siblings are HLA-identical in 75% of cases, confirming the association between HLA and IDDM, and suggesting recessively in inheritance of IDDM susceptibility. However, the most striking finding is that 52% of IDDM offspring are positive for both HLA-DRW3 and DRW4, compared with only 8% of their non-diabetic sibs and 1% of the general population. The risk for IDDM for the HLA-DRW3/DRW4 heterozygote is 37.2, and the chance that a child from a multiple-case family of IDDM will himself develop the disease is 6.5 times as great if he is a HLA-DRW3/DRW4 heterozygote than if he is not positive for both antigens. Possible genetic mechanisms are discussed, but the present data strongly support the interaction of two HLA-DR associated susceptibility genes in IDDM and rejects the hypothesis of a single autosomal recessive susceptibility gene.
在导致易感性的遗传机制数量得以阐明之前，胰岛素依赖型糖尿病（IDDM）的发病机制仍将不明。对澳大利亚IDDM的多病例家庭进行了IDDM和HLA单倍型一致性检查，并分析了其与一个或两个高危易感性基因假说的拟合优度。在75%的病例中，糖尿病同胞的HLA相同，这证实了HLA与IDDM之间的关联，并提示IDDM易感性的隐性遗传。然而，最显著的发现是，52%的IDDM后代HLA - DRW3和DRW4均为阳性，相比之下，其非糖尿病同胞中只有8%，普通人群中只有1%如此。HLA - DRW3/DRW4杂合子患IDDM的风险为37.2，IDDM多病例家庭中的孩子若为HLA - DRW3/DRW4杂合子，其患该病的几率是两种抗原均为阴性者的6.5倍。文中讨论了可能的遗传机制，但目前的数据有力地支持了IDDM中两个与HLA - DR相关的易感性基因的相互作用，并否定了单一常染色体隐性易感性基因的假说。
