V A Belo1, M R Luizon1, R Lacchini1, J A Miranda2, C M M Lanna3, D C Souza-Costa1, J E Tanus-Santos1. 1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil. 2. Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil. 3. Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
Abstract
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.
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 obesechildren 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:Obesechildren 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 obesechildren 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 obesechildren with ⩾ 3 MRFs. These results suggest that obesity and MRFs are more influential than genetic polymorphisms in the determination of visfatin/NAMPT levels in obesechildren. Further research is necessary to explain why the GG genotype is not associated with increased visfatin/NAMPT levels in obesechildren with ⩾ 3 MRFs.
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