PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children

Abstract

Obesity is associated with the changes of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNFalpha) and transforming growth factor beta (TGFbeta) levels. However, the precise effect of the 4G allele on obesity is still contradictory. Here, we aimed to elucidate the role of the 4G/5G polymorphism of the PAI-1 gene on the PAI-1 level and determine the associations between cytokines, glucose and lipid metabolism parameters in obese children. Thirty-nine obese children (mean age 11.4 +/- 3.3 years) and 38 age-matched healthy control group (mean age 10.3 +/- 3.5 years) were included in the study. In all cases, serum levels of glucose, lipid and insulin were measured, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, and 4G/5G polymorphism of PAI-1 gene, plasma PAI-1 level and serum TNFalpha and TGFbeta levels were studied. The mean relative body mass index (BMI) and HOMA-IR score, VLDL, TG, insulin, PAI-1, TNFalpha levels were higher, and HDL and TGFbeta levels were lower in the obese group. The frequency of the 4G/4G genotype was considerably higher in obese children than in controls. Also, a positive correlation was found between PAI-1 and TNFalpha levels, and relative BMI, HOMA-IR score, insulin, TG, HDL levels. TGFbeta was inversely correlated only with relative BMI. There was no correlation among three cytokines. In conclusion, childhood obesity contributes to higher PAI-1 and TNFalpha and lower TGFbeta levels. Especially PAI-1 and TNFalpha accompany insulin resistance and dyslipidemia.