Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Gene. 2013 Sep 25;527(2):545-52. doi: 10.1016/j.gene.2013.06.026. Epub 2013 Jun 21.
Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS).
The genotype frequency of PTEN -9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case-control analysis.
The PTEN -9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged <60 years or ≥60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P<0.05). In the <60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P<0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P=0.001) contributed independently to 4.2% (adjusted R(2)) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P=0.004), gender (P=0.000) and the PTEN polymorphism (P=0.032) contributed independently to 5.6% (adjusted R(2)) of WHtR variance.
The CG genotype of PTEN -9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.
磷酸酶与张力蛋白同源物基因(PTEN)作为抑癌基因,其功能障碍会影响胰岛素的功能已得到证实。然而,PTEN 单核苷酸多态性(SNP)与 IR 相关疾病的关联研究还很有限。本研究旨在探讨其多态性是否与代谢综合征(MetS)的发病风险有关。
采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)法检测了 530 例 MetS 患者和 202 例汉族健康对照者的 PTEN-9C>G 多态性的基因型频率,并进行病例对照分析。
PTEN-9C>G 多态性与 MetS 或其高血糖、高血压和高三酰甘油血症无关。在年龄<60 岁或≥60 岁的对照组中,CG 基因型个体的胰岛素敏感性低于 CC 基因型个体(P<0.05)。在<60 岁 MetS 组和正常糖耐量(NGT)亚组中,CG 个体的胰岛素敏感性较低,腰围(WC)和腰高比(WHtR)较高(P<0.05)。多元线性回归分析显示,PTEN 多态性(P=0.001)可独立解释 4.2%(校正 R(2))的胰岛素敏感性变异(由 Matsuda ISI 估计),而年龄(P=0.004)、性别(P=0.000)和 PTEN 多态性(P=0.032)可独立解释 5.6%(校正 R(2))的 WHtR 变异。
PTEN-9C>G 多态性的 CG 基因型与 MetS 及其部分成分无关。然而,它不仅可能降低健康对照组和老年前期或 NGT 患者的 MetS 中的胰岛素敏感性,而且可能增加这些 MetS 个体中心性肥胖的风险。