P46 - Genetic variants associated with obesity in patients undergoing bariatric surgery: a retrospective case series study

Background/Introduction Limited evidences support the role of specific genetic variants on the outcomes of metabolic bariatric surgery (MBS), partly due to study design limitations, sample size and selection, follow-up duration, gene selection, and genotyping methods. Identifying genetic variants influencing surgical outcomes could clarify the pathophysiological mechanisms of obesity, particularly in patients experiencing weight regain or insufficient weight loss after MBS. Purpose To determine the role of genetic variants in non-responders or poor responders to MBS. Methods We conducted a retrospective study on adult subjects (n=21) exhibiting weight regain or insufficient weight loss after MBS, with a minimum follow-up of three years, who underwent genetic testing for obesity. Weight regain was defined as excess weight loss (%EWL) <50% after initially achieving %EWL >50%. Insufficient weight loss was defined as %EWL <50% at 18 months post-MBS. Ideal body weight used to calculate %EWL was defined as the weight corresponding to a body mass index (BMI) of 25 kg/m2. Genetic testing included analysis of mutations in 79 obesity- associated genes and one chromosomal region. Results The study population comprised 21 subjects with a mean age of 44.39 years (range 31.84–58.29), 81% female, with a baseline mean BMI of 48.31 kg/m2 (range 38.8–66.3). Surgical procedures were 52% gastric bypass (GBP) and 48% sleeve gastrectomy (SG). The mean postoperative BMI nadir was 35.10 kg/m2 (range 26.6–48.5), reached after 20.61 ± 8.49 months from MBS. Genetic test results are available for 13 subjects to date. Heterozygous mutations were identified in 60% of subjects, including: a pathogenic variant in the PCSK1 gene; variants of unknown clinical significance in SH2B1 and POMC genes; potentially relevant variants in ALMS1, BBS10, and IFT172 (in the same subject), RAI and SEMA3F (in the same subject), SEMA3B and ADCY3; and likely benign variants in LEPR, PLXNA4, VPS13B, and PCNT genes. Conclusion(s) According to our data, it seems to exist a correlation between post- bariatric surgery weight regain and genetic.