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Associations of the PTEN − 9C>G polymorphism with insulin sensitivity and central obesity in Chinese
Authors:Qiu Yang,Hongyi Cao,Shugui Xie,Yuzhen Tong,Qibo Zhu,Fang Zhang,Qingguo Lü  ,Yan Yang,Daigang Li,Mei Chen,Changyong Yu,Wei Jin,Yuquan Yuan,Nanwei Tong
Affiliation:1. Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, China;2. Division of Endocrinology and Metabolism, Chengdu Fifth People''s Hospital, Chengdu, Sichuan, China;3. Chengdu Aerospace Hospital, Chengdu, Sichuan, China;4. Department of Clinical Medicine, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China;5. Chengdu Yincao Community Hospital, Chengdu, Sichuan, China
Abstract:

Background

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).

Methods

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.

Results

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 R2) 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 R2) of WHtR variance.

Conclusions

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.
Keywords:PTEN, phosphatase and tensin homolog on chromosome 10   SNP, single nucleotide polymorphism   MetS, metabolic syndrome   NGT, normal glucose tolerance   IR, insulin resistance   CVD, cardiovascular disease   PD, prediabetes   DM, type 2 diabetes mellitus   BMI, body mass index   WC, waist circumference   WHtR, waist circumference/height   Matsuda ISI, Matsuda insulin sensitivity index   HOMA-IR, homeostasis model assessments of insulin resistance   HOMA-β, homeostasis model assessments of β-cell function   PI3K, phosphatidylinositol (PI) 3-kinase   PIP2, phosphatidylinositol-4,5-bisphosphate   PIP3, phosphatidylinositol-3,4,5-trisphosphate   PKA, protein kinase A   PKC, protein kinase C   MMAC1, multiple advanced cancers 1   TEP1, TGFβ-regulated and epithelial cell-enriched phosphatase 1   NAFLD, nonalcoholic fatty liver disease   OGTT, oral glucose tolerance test   HbA1c, glycated hemoglobin   MALDI-TOF MS, Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry   ANOVA, analysis of variance   OR, odds ratio   CI, confidence interval
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