Background: Obesity is a metabolic disorder associated with increased PAI-1 levels in the circulation. This increase is related to insulin resistance and cardiovascular disease (CVD). In adults the relationship between plasma PAI-1 levels and the 4G/5G gene polymorphism in the PAI-1 gene has been demonstrated, but few data exist in children.
Objective and hypotheses: To assess the relationship between PAI-1 plasma levels and the PAI-1 4G allele gene polymorphism with family history of CVD, anthropometric and metabolic parameters in a sample of Greek children and adolescents.
Method: 195 subjects, 106 obese/overweight (median age 10.7 years, range 2.2517.41) and 89 non-obese controls (median age 10 years, range 3.7217.51) were studied. Serum levels of glucose, insulin, PAI-1 levels were measured, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, and the PAI-1 4G/5G gene polymorphism was studied by PCR-restriction fragment length polymorphism. Family history of cardiovascular disease (CVD) was obtained from all participants.
Results: The prevalence of insulin resistance (HOMA-IR) in the obese/overweight group was significantly higher (17.9%) than in the normal-weight group (7.8%) (P<0.05). Frequencies of the PAI-1 gene polymorphisms were 36.8% (4G/4G), 28.3% (4G/5G), 18.8% (5G/5G) in the obese/overweight group and 22.5% (4G/4G), 21.7% (4G/5G), 31.4% (5G/5G) in the control group. FH of CVD was positive in 67.9% (obese/overweight group) compared to 66.2% (controls), and statistically significant (P<0.05) in relation to the PAI-1 gene 4G/4G and 4G/5G polymorphisms (36.8, 28.3 and 22.5, 21.7% respectively). HOMA-IR and PAI-1 plasma levels were also significantly correlated in the obese/overweight group compared to controls (P<0.05).
Conclusion: In our obese children with FH of CVD and any feature of metabolic syndrome, the frequency of 4G/4G and 4G/5G genotype was significantly higher than the 5G/5G genotype in the PAI-1 gene. In this group of children high HOMA-IR value is an extra risk factor for developing vascular disease in adult life.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology