Plasminogen activator inhibitor-1 (PAI-1) gene polymorphism (-675 4G/5G) associated with obesity and vascular risk in children.

摘要

Atherothrombotic complications in insulin resistance are partly attributed to impaired fibrinolysis caused by increased PAI-1 plasma levels, and 4G/5G promotor polymorphism of the PAI-1 gene may modulate PAI-1 transcription. OBJECTIVE: To investigate PAI-1-675 4G/5G allele gene polymorphism and its relationship with obesity in children. CHILDREN AND METHOD: The study participants were 133 apparently healthy non-obese children, 24 probable exogenously obese without family history (Group I), 66 probable familial obese (Group II), and 44 obese children who were referred to the pediatric endocrinology department with any complication of obesity (Group III). Group I and Group II obese children were gathered from a school-based epidemiological study. RESULTS: Incidence of obesity was 19% in a school with high socio-economic status, whereas it was 4% in a school with low socio-economic status. Frequencies of 4G/4G gene polymorphisms were 24.81%, 37.50%, 64.80% and 61.11% in the control group, and groups I, II, and III, respectively. In groups II and III, 4G/4G gene polymorphism, and in non-obese control children 5G/5G gene polymorphism, was common. In obese children in the presence of family history for obesity and metabolic syndrome (odds ratio [OR]: 4.48, 95% confidence interval [CI]: 1.26-15.82), carriage of the 4G allele either in heterozygous or homozygous state increased the risk of vascular disease (OR: 6.10, 95% CI 1.64-22.90). In patients with acanthosis nigricans, high HOMA-IR values, hypertriglyceridemia and elevated atherogenic index, 4G/4G genotype frequency was remarkably higher compared to patients with other features of metabolic syndrome. CONCLUSION: The increasing prevalence of childhood obesity in high socio-economic status is associated with health risks. In obese children with family history of obesity and cardiovascular disease or type 2 diabetes mellitus and in obese children who had any feature of metabolic syndrome, frequency of 4G/4G genotype was more than the 4G/5G and 5G/5G genotypesin the PAI-1 gene. These patients can be at increased risk for developing vascular disease. Acanthosis nigricans, high HOMA-IR value, hypertriglyceridemia and high atherogenic index can also reflect the high risk of vascular disease in metabolic syndrome.