Polymorphism A36G of the tumor necrosis factor receptor 1 gene is associated with PAI-1 levels in obese women.
The tumor necrosis factor (TNF) pathway may be implicated in etiopathogenesis of PAI-1 overexpression during obesity. The aim of this study was to investigate the influence of polymorphism A36G of the TNF receptor 1 (TNFRSF1A +36A/G) on plasma concentrations of PAI-1 in 163 obese (31 with the metabolic syndrome, MetS) and 150 lean, healthy women. Genotypic and allele frequencies did not significantly differ between obese and lean subjects. TNFRSF1A genotypes were significantly associated with sTNFR1 plasma levels in obese women only (p < 0.01); TNFRSF1A +36G/G obese carriers exhibited higher sTNFR1 and PAI-1 levels than A carriers (p < 0.01 and p < 0.05, respectively). In obese women, the presence of the MetS significantly potentiated the elevation of sTNFR1 and PAI-1 levels observed in the TNFRSF1A + 36G/G carriers. Our results suggest that association between TNFRSF1A +36G/G genotype and the MetS renders obese women more prone to activation of the TNF pathway reflected by high circulating sTNFR1 and PAI-1 levels.
Mavri
Alenka
A
Inserm UMR 626 and Université de la Méditerranée, Marseille, France.
Bastelica
Delphine
D
Poggi
Marjorie
M
Morange
Pierre
P
Peiretti
Franck
F
Verdier
Monique
M
Juhan-Vague
Irène
I
Alessi
Marie-Christine
MC
D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D009765:Obesity / Q000097:blood / Q000209:etiology* / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D012995:Solubility
D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I