A variation in 3′ UTR of hPTP1B increases specific gene expression and associates with insulin resistance
A variation in 3′ UTR of hPTP1B increases specific gene expression and associates with insulin resistance
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DOI：
10.1086/339270
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发表时间：
2002-03-01
影响因子：
9.8
通讯作者：
Trischitta, V
中科院分区：
文献类型：
--
作者：
Di Paola, R;Frittitta, L;Trischitta, V
蛋白酪氨酸磷酸酶1B（PTP 1B）抑制胰岛素信号传导，当过度表达时，在胰岛素抵抗中发挥作用（Ahmad et al. 1997）。我们在PTP 1B基因的3'非翻译区中鉴定了一个1484 insG变异，该变异在两个不同人群中与胰岛素抵抗的几个特征相关：在男性个体中，胰岛素抵抗HOMA（IR）指数值较高，（P = 0.006），血清甘油三酯（P = 0.0002）和总/高密度脂蛋白胆固醇比率（P = 0.025），以及女性个体中较高的血压（P = 0.01）。在一项基于家族的关联研究中，通过使用基因型不一致的同胞对也获得了类似的数据（Gu et al. 2000）。携带1484 insG变体的受试者也显示骨骼肌中PTP 1B mRNA过表达（6，166 +/-1，879拷贝/40 ng RNA vs. 2，983 +/-1，620;）。最后，与转染野生型PTP 1B的人胚肾293细胞相比，转染1484 insG PTP 1B的人胚肾293细胞中PTP 1B mRNA的稳定性显著更高（P <0.01）。我们的数据表明，1484 insG等位基因导致PTP 1B过表达，并在胰岛素抵抗中发挥作用。因此，携带1484 insG变体的个体可能特别受益于PTP 1B抑制剂，这是一种有前途的治疗胰岛素抵抗的新工具（Kennedy和Ramachandran 2000）。
Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P = .006), serum triglycerides (P = .0002), and total/HDL cholesterol ratio (P = .025) and, among female individuals, higher blood pressure (P = .01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 +/- 1,879 copies/40 ng RNA vs. 2,983 +/- 1,620;). Finally, PTP1B mRNA stability was significantly higher (P < .01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).