A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes
A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes
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DOI：
10.1007/s00125-002-0803-z
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发表时间：
2002-05-01
期刊：
影响因子：
8.2
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Hara, K;Tobe, K;Kadowaki, T
目的/假设。过氧化物酶体增殖物激活受体γ共激活因子-1（PGC-1）是核受体PPARgamma的转录共激活因子，在适应性产热和胰岛素敏感性中发挥作用。血浆空腹胰岛素与PGC-1基因所在的染色体区域有关。因此，PGC-1可以被视为11型（非胰岛素依赖型）糖尿病易感基因的功能和位置候选者。在对PGC-1基因进行单核苷酸多态性（SNPs）筛查后，我们对537例11型糖尿病患者和417例非糖尿病受试者进行了相关性研究。在PGC-1基因中发现了3个相对常见的SNP（IVS 4 - 11 T> C、Thr 394 Thr和Gly 482 Ser）。空腹胰岛素有显著性差异（Gly/Gly; 37.7 +/- 1.43，Gly/Ser; 40.2 +/- 1.21，Ser/Ser; 44.3 +/- 1.82 pmol/l，p = 0.018）和胰岛素抵抗指数（Gly/Gly; 1.48 +/- 0.06，Gly/Ser; 1.56 +/- 0.05，Ser/Ser; 1.75 +/- 0.08，p = 0.027）。Thr 394 Thr-Gly 482 Ser单倍型与11型糖尿病相关（p = 0.00003）。本研究结果提示PGC-1基因可能参与了II型糖尿病的发病机制。
Aims/hypothesis. Peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARgamma, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type 11 (non-insulin-dependent) diabetes mellitus.Methods. After screening the PGC-1 gene for single nucleotide polymorphisms, (SNPs), we performed an association study using the newly detected SNPs in 537 Type 11 diabetic patients and 417 non-diabetic subjects.Results. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 +/- 1.43, Gly/Ser; 40.2 +/- 1.21, Ser/Ser; 44.3 +/- 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 +/- 0.06, Gly/Ser; 1.56 +/- 0.05, Ser/Ser; 1.75 +/- 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr - Gly482Ser haplotype was associated with Type 11 diabetes (p = 0.00003).Conclusion/interpretation. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.