Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors

Pediatr Diabetes. 2016 Dec;17(8):576-583. doi: 10.1111/pedi.12339. Epub 2015 Nov 26.

Abstract

Background: Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease.

Objectives: The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications.

Methods: Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, metabolic risk factors (blood pressure, triglycerides, high-density lipoprotein cholesterol, insulin resistance) and markers of vascular inflammation, such as high-sensitive C-reactive protein (hs-CRP), was tested.

Results: We found SNP rs3758538 to be associated with obesity (p = 0.007). Specifically, each copy of the minor allele C was associated with an increased risk of obesity, by more than twofold, in respect of being homozygous for the major allele A (odds ratio = 2.4; 95% confidence interval = 1.2-4.8). The rs3758538 and rs34571439 RBP4 SNPs correlated with plasma RBP4 levels. The SNPs rs12265684 and rs34571439 correlated with plasma triglyceride levels. The rs34571439 was also associated to hs-CRP levels. Marginal association of RBP4 SNPs with plasma high-density lipoprotein levels (rs34571439), blood pressure (rs12265684) and insulin resistance (rs3758539) was also observed.

Conclusions: These findings suggest that childhood obesity may be associated with variations in RBP4 gene. The presence of selective SNPs in the RBP4 gene may account for metabolic complications.

Keywords: C-reactive protein; RBP4; gene polymorphisms; lipids; obesity.

MeSH terms

  • Adolescent
  • Cardiovascular Diseases / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Pediatric Obesity / complications*
  • Pediatric Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Retinol-Binding Proteins, Plasma / genetics*
  • Risk Factors

Substances

  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma