The Effects of NAMPT Haplotypes and Metabolic Risk Factors on Circulating Visfatin/NAMPT Levels in Childhood Obesity
Overview
Affiliations
Objective: Polymorphisms in the NAMPT gene, which encodes the adipocytokine visfatin/nicotinamide phosphorybosil transferase (NAMPT), affect the circulating visfatin/NAMPT levels and are associated with obesity and cardiovascular diseases. However, no study has tested the hypothesis that NAMPT haplotypes could affect visfatin/NAMPT levels in case of childhood obesity. We investigated the effects of traditional metabolic risk factors (MRFs) and NAMPT polymorphisms T/C (rs1319501) and A/G (rs3801266) or haplotypes on visfatin/NAMPT levels in obese children and adolescents, and whether NAMPT polymorphisms and/or haplotypes are associated with susceptibility to childhood obesity.
Methods: We studied 175 control, 99 obese and 82 obese with ⩾ 3 MRFs children and adolescents. Genotypes were determined by a Taqman allele discrimination assay and real-time PCR. The plasma visfatin/NAMPT level was measured using an enzyme immunoassay.
Results: Obese children and adolescents with ⩾ 3 MRFs had higher plasma visfatin/NAMPT levels in comparison with control children and adolescents (P<0.05). Although positive associations were observed between visfatin/NAMPT and body mass index (rs = 0.157; P = 0.034) as well as visfatin/NAMPT and waist circumference (rs = 0.192; P = 0.011), visfatin/NAMPT and high-density lipoprotein cholesterol were inversely associated (rs = -0.162; P = 0.031). No significant differences in genotype, allele or haplotype frequency distributions for the studied polymorphisms were found when the three groups were compared. However, higher plasma visfatin/NAMPT levels were found in control and obese subjects carrying the GG genotype for the A/G (rs3801266) polymorphism (P<0.05) but not in obese children with ⩾ 3 MRFs. Moreover, control subjects carrying the 'T-G' haplotype showed higher plasma visfatin/NAMPT levels. NAMPT genotypes or haplotypes were not associated with childhood obesity.
Conclusions: Obesity in children with ⩾ 3 MRFs increases plasma visfatin/NAMPT levels, and this marker was associated with body mass index and waist circumference. The A/G polymorphism and NAMPT haplotypes affect plasma visfatin/NAMPT levels in controls but not in obese children with ⩾ 3 MRFs. These results suggest that obesity and MRFs are more influential than genetic polymorphisms in the determination of visfatin/NAMPT levels in obese children. Further research is necessary to explain why the GG genotype is not associated with increased visfatin/NAMPT levels in obese children with ⩾ 3 MRFs.
Mocnik M, Zagradisnik B, Marcun Varda N Children (Basel). 2022; 9(8).
PMID: 36010152 PMC: 9406300. DOI: 10.3390/children9081262.
Visfatin: A Possible Role in Cardiovasculo-Metabolic Disorders.
Dakroub A, Nasser S, Younis N, Bhagani H, Al-Dhaheri Y, Pintus G Cells. 2020; 9(11).
PMID: 33182523 PMC: 7696687. DOI: 10.3390/cells9112444.
Javanmard S, Dehghananzadeh R, Rafiee L, Naji H, Rezayat A, Sarrafzadegan N J Res Med Sci. 2017; 21:105.
PMID: 28250782 PMC: 5322690. DOI: 10.4103/1735-1995.193177.
Luizon M, Palei A, Belo V, Amaral L, Lacchini R, Duarte G Pharmacogenomics J. 2016; 17(5):427-434.
PMID: 27168100 DOI: 10.1038/tpj.2016.35.
Larrad M, Anchuelo A, Fernandez Perez C, Perez Barba M, Lazcano Redondo Y, Serrano Rios M PLoS One. 2016; 11(5):e0153976.
PMID: 27166797 PMC: 4864316. DOI: 10.1371/journal.pone.0153976.