SERPINE-1 Gene Methylation and Protein as Molecular Predictors of Laparoscopic Sleeve Gastrectomy Outcome

Abstract

Body weight is subjected to genetic and epigenetic modifiers that might affect the success of weight loss interventions. Because of its possible complications and disparity in patients' response, identification of predictors to the outcome of bariatric surgery is indispensable. This prospective study aims to investigate serpin peptidase inhibitor type 1 (SERPINE-1) protein and gene methylation as molecular predictors to the outcome of bariatric surgery. One hundred participants were enrolled and divided to control group (n = 50) and obese patients who underwent laparoscopic sleeve gastrectomy (LSG) (n = 50). Anthropometric measurements were assessed and blood samples were collected preoperatively and 6months postoperatively for assessment of SERPINE-1 protein and gene methylation, C-reactive protein (CRP), and homeostatic model assessment of insulin resistance (HOMA-IR). Moreover, subjects were followed for 2years for weight loss parameters. Patients with obesity showed high baseline SERPINE-1 protein and gene hypermethylation where LSG was followed by a drop in SERPINE-1 protein level but not gene hypermethylation. Baseline SERPINE-1 gene methylation was negatively related to postoperative weight loss and was the independent predictor to weight loss after LSG. Likewise, postoperative SERPINE-1 protein was negatively related to weight loss with independent expression from its gene methylation state. Furthermore, postoperative SERPINE-1 gene methylation correlated to CRP and HOMA-IR. Baseline SERPINE-1 gene methylation might be a predictor of weight loss after LSG. Meanwhile, postoperative SERPINE-1 protein could be a predictor to weight loss maintenance after LSG. Lastly, postoperative SERPINE-1 gene methylation might serve as an index to postoperative changes in obesity-related comorbidities.