Analysis of Endothelial Protein C Receptor Gene and Metabolic Profile in Prader‐Willi Syndrome and Obese Subjects

Abstract

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.

Phase Angle: Could Be an Easy Tool to Detect Low-Grade Systemic Inflammation in Adults Affected by Prader–Willi Syndrome?

“…This LGI is closely linked to the development of several metabolic and cardiovascular diseases, also in PWS adults [ 67 , 68 , 69 ]. In our results, we reported that the hs-CRP levels were higher in PWS adults than in the control group, and this is in agreement with other studies performed in PWS adults [ 7 , 8 , 70 , 71 ]. Based on these results, we speculate that the PWS adults with the highest values of hs-CRP levels as inflammatory marker were those with lower cellular health, expressed as a smaller PhA.…”

The genetic background and vitamin D supplementation can affect irisin levels in Prader–Willi syndrome

“…The present study displayed that PWS patients has comparable levels of irisin with respect to the controls; interestingly, a deepened analysis showed that both pediatric and adult PWS with DEL15 have significantly reduced levels of irisin compared with the controls, suggesting that the genetic background could be associated with a different metabolic profile in PWS [ 32 ]. Additionally, we also showed that patients who did not receive vitamin D supplementation had low serum levels of irisin, despite having the UPD as genetic alterations.…”

Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health

“…However, metabolic alteration in PWS patients is debated and it has been reported that despite major adiposity, PWS patients exhibit relative improved insulin sensitivity compared with subjects with common obesity. [13][14][15][16] Many features in PWS patients could affect glucose homeostasis, including decreased baseline insulin levels, 16 17 increased levels of the insulin sensitising hormone adiponectin, 16 17 different body distribution of adipose tissue and an increased subcutaneous adipose tissue expandability with decreased inflammation and fibrosis, 16 but the mechanism underlying the improved glucose metabolism of PWS patients remains elusive. We here used PWS as a model of genetically induced severe obesity with improved insulin resistance to investigate how the interaction between genetics and gut microbiota can affect individual metabolic status.…”