Curie-Cohen M
Tissue Antigens. 1981 Feb;17(2):136-48. doi: 10.1111/j.1399-0039.1981.tb00678.x.
The relative risk of B8/B15 heterozygotes for juvenile-onset diabetes is higher than the risk for people having B8 or B15 alone. This has been cited as evidence for genetic heterogeneity in juvenile diabetes. However, the observed relative risks are compatible with a single susceptibility allele. If disease susceptibility is recessive, for example, then an individual with two disease associated antigens is more likely to be susceptible than an individual with only one associated antigen. The relative risk for an HLA heterozygote should be intermediate between that of the respective homozygotes, so that an interaction effect of two alleles can only be supported if the heterozygote risk is significantly greater than both homozygote risks. The estimated relative risks for B8 and B15 homozygotes, based on data from four different populations, is approximately equal to the risk for B8/B15 heterozygotes. Moreover, disease manifestations which are differentially associated with B8 and B15, such as antibody production to exogenous insulin, may be due to linkage disequilibrium between HLA and other loci which are not directly related to susceptibility of juvenile diabetes. Therefore, while the susceptibility to juvenile diabetes may have several genetic forms, there is no support for distinct B8-associated and B15-associated forms of susceptibility.
B8/B15杂合子患青少年型糖尿病的相对风险高于仅携带B8或B15的人群。这一点被引为青少年糖尿病存在基因异质性的证据。然而，观察到的相对风险与单一易感等位基因相符。例如，如果疾病易感性是隐性的，那么拥有两种与疾病相关抗原的个体比仅拥有一种相关抗原的个体更易患病。HLA杂合子的相对风险应介于各自纯合子的风险之间，因此，只有当杂合子风险显著高于两个纯合子风险时，才能支持两个等位基因的相互作用效应。基于四个不同人群的数据估算，B8和B15纯合子的相对风险约等于B8/B15杂合子的风险。此外，与B8和B15有不同关联的疾病表现，如对外源胰岛素产生抗体，可能是由于HLA与其他与青少年糖尿病易感性无直接关联的基因座之间的连锁不平衡所致。因此，虽然青少年糖尿病的易感性可能有多种遗传形式，但并不支持存在与B8相关和与B15相关的不同易感性形式。
