title: Association between CETP gene polymorphism, insulin resistance and risk of diabetes mellitus in patients with vascular disease.
abstract: BACKGROUND
  Genetic inhibition of Cholesteryl Ester Transfer Protein (CETP) might be associated with insulin resistance and incident type 2 diabetes mellitus (T2DM). This study investigated the relation between a genetic variant in the CETP gene and measures of insulin resistance and incident T2DM in patients with manifest cardiovascular disease (CVD). Furthermore the effect on risk of recurrent cardiovascular events was investigated.
  
  
  METHODS
  SMART is a prospective cohort study performed in 5601 patients with clinically manifest CVD. We selected a variant (rs3764261) associated with reduced CETP activity and increased levels of HDL cholesterol (HDL-C). Patients were divided in three groups: 2640 wild type patients (GG), 2420 heterozygotes for rs3764261 (GT) and 541 homozygotes for rs3764261 (TT). Regression analyses were performed using an additive model.
  
  
  RESULTS
  The study population consisted of 4656 patients without T2DM and 945 patients with T2DM at baseline. Presence of rs3764261 was associated with increased HDL-C in patients without T2DM (β 0.106, 95%CI 0.083-0.128) and with T2DM (β 0.043, 95%CI 0.007-0.078). During a median follow up of 7.2 years (IQR 4.7-10.2) 427 incident T2DM occurred. Presence of rs3764261 was not related to incident T2DM (HR 0.96, 95%CI 0.83-1.11) in patients without T2DM at baseline. Furthermore, presence of rs3764261 was not related to insulin resistance (glucose, insulin, HOMA-IR, HbA1c) or recurrent CVD (HR 0.92, 95%CI 0.84-1.02).
  
  
  CONCLUSIONS
  Presence of CETP SNP rs3764261 is not associated with insulin resistance and incident T2DM in patients with clinically manifest vascular disease. Furthermore, no effect of rs3764261 on the risk of recurrent CVD was observed.
authors: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Charlotte
authors: C
authors: Koopal
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Yolanda
authors: Y
authors: van der Graaf
authors: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom.
authors: Folkert W
authors: FW
authors: Asselbergs
authors: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jan
authors: J
authors: Westerink
authors: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: F.L.J.Visseren@umcutrecht.nl.
authors: Frank L J
authors: FL
authors: Visseren
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D048909:Diabetes Complications / Q000097:blood / Q000235:genetics; D003920:Diabetes Mellitus / Q000097:blood* / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012008:Recurrence; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D014280:Triglycerides / Q000378:metabolism; D014652:Vascular Diseases / Q000097:blood* / Q000150:complications / Q000235:genetics
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D014280:Triglycerides
keywords: Cardiovascular disease; Cholesteryl ester transfer protein (CETP); Diabetes mellitus type 2; Insulin resistance; Single nucleotide polymorphism (SNP)