Associations of the PTEN -9C>G polymorphism with insulin sensitivity and central obesity in Chinese

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 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.

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