title: Arg(972) insulin receptor substrate-1 is associated with elevated plasma endothelin-1 level in hypertensives.
abstract: OBJECTIVE
  To explore the association among Arg(972) insulin receptor substrate-1 (IRS-1), hypertension, insulin resistance, and plasma levels of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1).
  
  
  METHODS
  A total of 1030 patients, including 521 healthy controls, 142 patients with both primary hypertension and insulin resistance, 184 patients with primary hypertension but no insulin resistance, and 183 patients with insulin resistance but no hypertension were genotyped for the Arg(972) IRS-1 polymorphism. Serum levels of ET-1 and eNOS were determined by ELISA. Shear stress was applied to human umbilical vein endothelial cells (HUVECs) overexpressing wild type IRS-1 or Arg(972) IRS-1, and the mRNA and secreted protein levels of ET-1 were measured by real-time RT-PCR and ELISA, respectively.
  
  
  RESULTS
  There was no significant difference in allelic frequency between patients with and without primary hypertension or insulin resistance, in the hypertensives, heterozygous Arg(972) IRS-1 carriers had significantly higher plasma ET-1 levels and blood pressure (BP) than the homozygous carriers. Although shear stress decreased ET-1 expression in control HUVECs as well as cells transfected with wild type Arg(972) IRS-1, it increased the mRNA dose-dependently and secreted protein levels of ET-1 in cells transfected with Arg(972) IRS-1.
  
  
  CONCLUSIONS
  Based on both in-vivo and in-vitro data, we have shown a potential causal association between Arg(972) IRS-1 and elevated plasma ET-1 level in hypertensives, which may account for the aggravated hypertension observed in hypertensives with heterozygous Arg(972) IRS-1. This study for the first time provides insights into the role of Arg(972) IRS-1 in hypertension.
authors: Department of Intensive Medicine, Guangdong General Hospital, Guangzhou, Guangdong, China.
authors: Cheng
authors: C
authors: Huang
authors: Zhanyi
authors: Z
authors: Lin
authors: Yingling
authors: Y
authors: Zhou
authors: Ming
authors: M
authors: Fang
authors: Suo
authors: S
authors: Sun
authors: Wenxin
authors: W
authors: Jiang
authors: Haojian
authors: H
authors: Dong
authors: Bo
authors: B
authors: Lv
authors: Huilan
authors: H
authors: Lan
authors: Miao
authors: M
authors: Chen
authors: Tianlun
authors: T
authors: Yang
authors: Hongke
authors: H
authors: Zeng
authors: Jiyan
authors: J
authors: Chen
mesh_terms: D001120:Arginine / Q000737:chemistry*; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D017931:DNA Primers; D018076:DNA, Complementary; D019332:Endothelin-1 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D055504:Insulin Receptor Substrate Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D019332:Endothelin-1; D055504:Insulin Receptor Substrate Proteins; D001120:Arginine; D052250:Nitric Oxide Synthase Type III