title: Visfatin and its genetic variants are associated with obesity-related morbidities and cardiometabolic risk in severely obese children.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: S Q
authors: SQ
authors: Ooi
authors: R M E
authors: RM
authors: Chan
authors: L K S
authors: LK
authors: Poh
authors: K Y
authors: KY
authors: Loke
authors: C K
authors: CK
authors: Heng
authors: Y H
authors: YH
authors: Chan
authors: S U
authors: SU
authors: Gan
authors: K O
authors: KO
authors: Lee
authors: Y S
authors: YS
authors: Lee
mesh_terms: D015502:Absorptiometry, Photon; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000209:etiology; D002648:Child; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D009767:Obesity, Morbid / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human
keywords: Adipokine; obese children; obesity; visfatin