Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects

Exp Diabetes Res. 2012:2012:827172. doi: 10.1155/2012/827172. Epub 2012 Oct 23.

Abstract

Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previously reported to be associated with hypertension. Moreover, the SNPs were tested for association with hemodynamic parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs11191548 (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic subjects showed a modest association with hypertension (P = 0.0265, 0.0020, 0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated with augmentation index in diabetic subjects who were not taking antihypertensive medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects receiving antihypertensive medication. This finding suggests that certain genetic variations found in diabetic subjects may confer arterial stiffness and the development of hypertension and also be affected by antihypertensive medication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / genetics*
  • Diabetic Angiopathies / metabolism
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prediabetic State / blood
  • Prediabetic State / complications*
  • Pulse Wave Analysis
  • Republic of Korea
  • Steroid 17-alpha-Hydroxylase / genetics*
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Vascular Stiffness*

Substances

  • Antihypertensive Agents
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase