Undlien D E, Bennett S T, Todd J A, Akselsen H E, Ikäheimo I, Reijonen H, Knip M, Thorsby E, Rønningen K S
Institute of Transplantation Immunology, National Hospital of Norway, Oslo.
Diabetes. 1995 Jun;44(6):620-5. doi: 10.2337/diab.44.6.620.
The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at -23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the -23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2.
已知与胰岛素依赖型糖尿病（IDDM）易感性相关的位于11号染色体p15.5区域的基因，最近被定位到一个包含胰岛素基因的4.1千碱基区域。该区域包含10个处于强连锁不平衡状态的候选多态性位点。通过对芬兰白种人IDDM患者和对照受试者的这10个多态性位点中的7个以及酪氨酸羟化酶微卫星进行基因分型，我们发现，在其他白种人群体中发现的许多与IDDM相关的多态性位点，在这个芬兰人群体中并未显示出任何关联。在所检测的多态性位点中，只有 -23 Hph I位点和串联重复序列可变数目（VNTR）位点具有显著的相对风险。此外，我们已经证明 -23 Hph I多态性无法解释这种关联。此处观察到的基因型模式与之前的比较表明，VNTR是IDDM2最有可能的候选基因。VNTR位于影响胰岛素基因表达的特定调控DNA序列附近，这表明它可能对胰岛素或其邻近基因之一（酪氨酸羟化酶或胰岛素样生长因子2）的表达产生影响。
