GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness?

Cardiovasc Diabetol. 2010 Nov 29:9:79. doi: 10.1186/1475-2840-9-79.

Abstract

Background: Recent studies revealed that glucokinase regulatory protein (GCKR) variants (rs780094 and rs1260326) are associated with serum triglycerides and plasma glucose levels. Here we analyzed primarily the association of these two variants with the lipid profile and plasma glucose levels in Hungarian subjects with type 2 diabetes mellitus and metabolic syndrome; and also correlated the genotypes with the carotid intima-media thickness records.

Methods: A total of 321 type 2 diabetic patients, 455 metabolic syndrome patients, and 172 healthy controls were genotyped by PCR-RFLP.

Results: Both GCKR variants were found to associate with serum triglycerides and with fasting plasma glucose. However, significant association with the development of type 2 diabetes mellitus and metabolic syndrome could not be observed. Analyzing the records of the patients, a positive association of prevalence the GCKR homozygous functional variants and carotid intima-media thickness was found in the metabolic syndrome patients.

Conclusions: Our results support that rs780094 and rs1260326 functional variants of the GCKR gene are inversely associated with serum triglycerides and fasting plasma glucose levels, as it was already reported for diabetic and metabolic syndrome patients in some other populations. Besides this positive replication, as a novel feature, our preliminary findings also suggest a cardiovascular risk role of the GCKR minor allele carriage based on the carotid intima-media thickness association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Carotid Arteries / diagnostic imaging*
  • Case-Control Studies
  • Chi-Square Distribution
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnostic imaging
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Hungary
  • Logistic Models
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / diagnostic imaging
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Triglycerides / blood
  • Tunica Intima / diagnostic imaging*
  • Tunica Media / diagnostic imaging*
  • Ultrasonography

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Blood Glucose
  • GCKR protein, human
  • Triglycerides