Visfatin and its genetic variants are associated with obesity-related morbidities and cardiometabolic risk in severely obese children

Pediatr Obes. 2014 Apr;9(2):81-91. doi: 10.1111/j.2047-6310.2013.00149.x. Epub 2013 Feb 28.

Abstract

Background: Visfatin is an adipokine, associated with obesity and possibly glucose regulation.

Objective: The aim of this study was to examine the association of visfatin and its genetic variants with adiposity, cardiometabolic risk factors and obesity-related morbidities in obese children.

Methods: Anthropometric measurements, dual energy X-ray absorptiometry scan, fasting blood samples and oral glucose tolerance tests were performed for 243 obese children. We screened the visfatin gene of 24 obese subjects and then performed genotyping of identified genetic variants in other 219 obese children through direct DNA sequencing.

Results: Fasting serum visfatin correlated with measures of obesity and liver enzymes and was elevated in obese children with abnormal glucose tolerance and non-alcoholic fatty liver disease. The two upstream single nucleotide polymorphisms, -3187G>A (rs11977021) and -1537C>T (rs61330082), were at complete linkage disequilibrium. The AA genotype of -3187G>A was associated with higher serum visfatin (6.17 ± 0.76 ng mL(-1) vs. 3.92 ± 0.44 ng mL(-1)) and higher triglyceride (1.39 ± 0.08 mmol L(-1) vs. 1.19 ± 0.07 mmol L(-1)) as compared with the GG genotype. There was also a significant linear increase in serum visfatin across GG to GA to AA genotype of -3187G>A, indicating possible additive effect of A allele. The dominant GA + AA genotype model of +21426G>A (rs2302559) was associated with lower serum visfatin (3.83 ± 0.56 ng mL(-1) vs. 5.13 ± 0.34 ng mL(-1)) and lower plasma glucose (4.37 ± 0.08 mmol L(-1) vs. 4.77 ± 0.12 mmol L(-1)) as compared with the GG genotype.

Conclusion: Visfatin and its genetic variants were associated with adiposity, obesity-related morbidities and adverse cardiometabolic parameters. This supported our hypothesis that visfatin plays a significant role in the development of obesity-related morbidities and cardiometabolic risk.

Keywords: Adipokine; obese children; obesity; visfatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Blood Glucose / metabolism
  • Body Mass Index
  • Cardiovascular Diseases / etiology
  • Child
  • Cytokines / blood
  • Cytokines / genetics*
  • Diabetic Angiopathies / etiology*
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / physiopathology
  • Female
  • Genetic Variation
  • Genotype
  • Glucose Tolerance Test
  • Humans
  • Linkage Disequilibrium
  • Male
  • Nicotinamide Phosphoribosyltransferase / blood
  • Nicotinamide Phosphoribosyltransferase / genetics*
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Obesity, Morbid / complications*
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / physiopathology
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Sequence Analysis, DNA

Substances

  • Blood Glucose
  • Cytokines
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human