The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus
The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus
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DOI：
10.1007/s10038-004-0158-z
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Matsumoto, N
中科院分区：
文献类型：
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作者：
Kamimura, J;Wakui, K;Matsumoto, N
2型糖尿病（T2 DM）是一组多因素疾病，由于胰岛素分泌或作用缺陷。尽管对2型糖尿病的遗传学研究很多，但其发病机制仍不清楚。我们发现了一个与平衡相互易位t（3;9）（p21.31;q33.1）相关的T2 DM家族。为了分离T2 DM易感的候选基因，我们构建了覆盖该家族中易位的3 p和9 q断裂点的物理图谱。因此，发现肌醇六磷酸激酶1基因（IHPK 1）（OMIM *606991）在3p21.31断点处被破坏。然后，我们对405例无关的T2 DM患者的IHPK 1的所有编码区进行了序列分析，以验证该基因的畸变是否在T2 DM患者中常见，但我们未能检测到任何致病性变化。IHPK 1或受易位位置效应影响的另一易感基因的破坏可能至少在该家族中解释T2 DM表型。或者，家族中IHPK 1的破坏是一种偶然关联。
Type 2 diabetes mellitus (T2DM) is a group of multifactorial disorders due to either defective insulin secretion or action. Despite the fact that numerous genetic researches of T2DM have been pursued, the pathogenic mechanisms remain obscure. We encountered a T2DM family associated with a balanced reciprocal translocation, t(3;9)(p21.31;q33.1). To isolate a candidate gene susceptible to T2DM, we constructed physical maps covering both the 3p and 9q breakpoints of the translocation in the family. Consequently, the inositol hexaphosphate kinase 1 gene (IHPK1) (OMIM *606991) was found to be disrupted at the 3p21.31 breakpoint. We then carried out sequence analysis for all coding regions of IHPK1 in 405 unrelated T2DM patients in order to validate whether aberrations of the gene are common in T2DM patients, but we failed to detect any pathogenic changes. The disruption of IHPK1 or another predisposing gene affected by position effect of the translocation may explain the T2DM phenotype at least in this family. Alternatively, the IHPK1 disruption in the family is a chance association.