Rowe R E, Wapelhorst B, Bell G I, Risch N, Spielman R S, Concannon P
Nat Genet. 1995 Jun;10(2):240-2. doi: 10.1038/ng0695-240.
Insulin-dependent diabetes mellitus (IDDM) is characterized by autoimmune destruction of the insulin secreting beta-cells of the pancreas and subsequent disruption of glucose metabolism. The tendency of IDDM to cluster in families and the modest (36%) concordance rate in monozygotic twins indicates that both genetic and environmental factors contribute to IDDM susceptibility. Recent genome-wide searches using the affected sib-pair (ASP) approach have provided evidence for novel loci, in addition to HLA (IDDM1) and insulin (IDDM2), which show evidence of linkage to IDDM (P < 0.05). We have evaluated 35 microsatellite marker loci on human chromosome 7 for linkage to IDDM in 339 affected sib-pair families. Increased sharing of parental haplotypes in affected sib-pairs was detected for two microsatellite markers flanking glucokinase (GCK). Preferential transmission of alleles to affected offspring was observed at one of these marker loci, GCK3, indicating linkage disequilibrium between the marker and a disease susceptibility locus. This combination of linkage and disease association suggests that glucokinase, or a gene in the vicinity, plays an important part in IDDM susceptibility.
胰岛素依赖型糖尿病（IDDM）的特征是胰腺中分泌胰岛素的β细胞发生自身免疫性破坏，随后葡萄糖代谢紊乱。IDDM在家族中具有聚集倾向，且同卵双胞胎的一致率适中（36%），这表明遗传和环境因素均对IDDM易感性有影响。最近使用受累同胞对（ASP）方法进行的全基因组搜索除了发现与IDDM相关的HLA（IDDM1）和胰岛素（IDDM2）外，还为新的基因座提供了证据，这些基因座显示出与IDDM的连锁证据（P < 0.05）。我们评估了人类7号染色体上的35个微卫星标记基因座与339个受累同胞对家族中IDDM的连锁情况。在葡萄糖激酶（GCK）两侧的两个微卫星标记中，检测到受累同胞对中亲代单倍型的共享增加。在其中一个标记基因座GCK3处观察到等位基因向受累后代的优先传递，这表明该标记与疾病易感基因座之间存在连锁不平衡。这种连锁和疾病关联的组合表明，葡萄糖激酶或其附近的一个基因在IDDM易感性中起重要作用。
