RESUMEN
Obese children have a great risk of hypertension and cardiovascular morbidity in adults. The insulin-like growth factor type II (IGF-II) regulates glucose homeostasis, cardiovascular functions, and lipid metabolism. IGF2 gene variants have shown a strong association with weight, body mass index (BMI), and metabolic profile in adults. We performed the molecular screening of two IGF2 polymorphisms (6815 A/T, 820 G/A), in 227 obese children to evaluate the potential association between IGF2 variants with either obesity or high blood pressure (assessed with a 24-h holter system) or both. A second cohort of age-, sex-, and BMI-matched children were enrolled to confirm any eventual association. We observed a significant association between the 6815 A/T IGF2 gene variant and high systolic blood pressure in obese children. Homozygote subjects for the T6815 allele showed, even in 24-h measurements, a higher risk to develop hypertension than those carrying the A6815 allele (OR = 3.7, 95% CI: 1.59-8.66). This result was confirmed in the second cohort (OR = 4.1, 95% CI: 1.41-6.50). Any statistically significant difference in terms of BMI between the genotype groups was observed. Our results suggest that IGF2 gene variants are involved in the blood pressure regulation in obese children.
Asunto(s)
Hipertensión/genética , Factor II del Crecimiento Similar a la Insulina/genética , Obesidad/genética , Adolescente , Índice de Masa Corporal , Peso Corporal , Niño , Estudios de Cohortes , Metabolismo Energético/fisiología , Humanos , Hipertensión/etiología , Italia , Modelos Logísticos , Obesidad/complicaciones , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
The endothelial protein C receptor (EPCR) has a critical role in the regulation of anticoagulant and anti-inflammatory functions of activated protein C (APC). Abnormalities in EPCR might be associated with an increased risk of thrombosis. In this respect, a 23 bp insertion in the exon 3 of the EPCR gene predicts a truncated protein which cannot bind APC. High levels of C-reactive protein (CRP), a strong predictor of cardiovascular events, are found both in the obese and in subjects with Prader-Willi syndrome (PWS). Several cardiovascular risk factors are already present in prepubertal PWS children, but it is uncertain which mechanism contributes to the increased risk of cardiovascular disease in PWS. We analyzed the distribution of 23 bp insertion in the EPCR gene in 81 overweight and obese PWS subjects, 52 adults and 29 children, and in 58 overweight and obese children and adolescents (controls). We found that 1/58 (1.7%) of the controls was heterozygous for the 23 bp insertion, while this mutation was never found in PWS subjects. Furthermore, we evaluated CRP levels, glucose, insulin, and lipid profile, and we found higher CRP values in PWS adults with respect to children with PWS and controls, and a better insulin sensitivity in all PWS subjects than in the controls. This study suggests that in PWS subjects there is no predisposition to develop thrombotic events in association with EPCR gene alteration and demonstrates substantial differences regarding metabolic and inflammatory profile between PWS and non-PWS obese children, with further impairment in adults with PWS.