Insulin-gene sharing in sib pairs with insulin-dependent diabetes mellitus: no evidence for linkage.
Insulin-gene sharing in sib pairs with insulin-dependent diabetes mellitus: no evidence for linkage.
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DOI：
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发表时间：
1988
影响因子：
9.8
通讯作者：
N. Cox;L. Baker;R. Spielman
中科院分区：
文献类型：
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作者：
N. Cox;L. Baker;R. Spielman
胰岛素依赖型糖尿病(IDDM)与胰岛素基因附近的RFLP之间的关联一直被观察到，但其病因学意义尚不清楚。我们研究了无关的IDDM患者(N=45)和对照组(N=65)，以确认这种关联--并评估了至少有两个受影响的(IDDM)同胞的22个家庭的关联证据--以确定胰岛素基因区域是否确实与IDDM的易感性有关。对所有个体进行胰岛素基因(5‘FP)5’侧翼区的RFLP分型，对与5‘FP连锁信息不全的12个家系进行额外紧密连锁的RFLP分型。我们发现IDDM患者5‘FP类1等位基因的频率(0.83)高于对照组(0.75)，这与已报道的关联一致，但在我们的样本中差异不具有统计学意义。在22个家系的33个受影响的同胞配对(Asp)中，如果假设最大可能共享，当共享不明确时，10对共享两个双亲胰岛素基因，17对共享一个，6对不共享。这种分布与紧密连锁不相容。相比之下，对于所有22个家系都具有充分信息的人类白细胞抗原区域，33个天冬氨酸转运蛋白中有19个共享两种单倍型，其余14个共享一种单倍型。没有一对既不是人类白细胞抗原单倍型，也不是人类白细胞抗原单倍型。因此，尽管这些数据清楚地说明了人类白细胞抗原相关的易感性对IDDM的贡献，但他们强烈反对胰岛素基因区域也有类似的贡献。
An association between insulin-dependent diabetes mellitus (IDDM) and an RFLP adjacent to the insulin gene has been consistently observed, but its etiological significance is unclear. We studied unrelated IDDM patients (N = 45) and controls (N = 65) to confirm the association--and assessed evidence for linkage in 22 families with at least two affected (IDDM) sibs--to determine whether the insulin-gene region actually contributes to susceptibility to IDDM. All individuals were typed for the RFLP in the 5'-flanking region of the insulin gene (5'FP) used in the previous studies, and the 12 families not fully informative for linkage with the 5'FP were typed for additional closely linked RFLPs. We found a higher frequency of class 1 alleles of the 5'FP in IDDM patients (.83) than in controls (.75), which is consistent with the reported association, but the difference was not statistically significant in our sample. Among the 33 affected sib pairs (ASPs) in 22 families, if maximum possible sharing is assumed when sharing is ambiguous, 10 pairs share both parental insulin genes, 17 pairs share one, and six share neither. This distribution is incompatible with close linkage. In contrast, for the HLA region, for which all 22 families are fully informative, 19 of the 33 ASPs share two haplotypes and the remaining 14 share one. There are no pairs that share neither HLA haplotype. Thus, although these data clearly illustrate the contribution of HLA-linked susceptibility to IDDM, they argue strongly against a contribution of similar magnitude by the insulin-gene region.