Longitudinal analysis of weight regain after Roux-en-Y gastric bypass ‒ The role of the MTCH2 gene polymorphism and dietary factors

Nutr Hosp. 2026 Mar 25. doi: 10.20960/nh.06238. Online ahead of print.

Abstract

Introduction: Roux-en-Y gastric bypass (RYGB) is a highly effective intervention for morbid obesity; however, significant inter-individual variability in long-term weight outcomes and the phenomenon of weight regain remain clinical challenges. Understanding the genetic and dietary factors influencing these variable responses is crucial for personalized patient management.

Objectives: this study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on weight loss response in morbidly obese patients undergoing bariatric surgery.

Material and methods: adults (n = 108) undergoing RYGB with five-year follow-up were included. Retrospective analysis covered anthropometric, body composition, dietary intake, and biochemical data. Genetic analysis (Illumina® BeadChip) from whole blood DNA identified obesity-related biomarkers. Standard statistical tests (p < 0.05) and bioinformatics software were utilized.

Results: significant and sustained improvements were observed across anthropometric and biochemical parameters post-RYGB. However, weight regain became evident from the second postoperative year. The T allele of the MTCH2 gene SNP rs3817334 was found to be prevalent in the cohort (42.4 %). Patients carrying at least one T allele exhibited significantly higher body mass index (BMI) and waist circumference (WC) at specific postoperative time points and a greater percentage of weight regain (> 10 % from nadir weight) at five years post-surgery (p = 0.004) compared to those with the CC genotype. No significant associations were observed with dietary intake or biochemical markers.

Conclusions: RYGB promotes substantial long-term weight loss, but weight regain is a notable concern from the second year. The MTCH2 gene SNP rs3817334, particularly its T allele, is associated with higher BMI and WC and contributes to a greater predisposition to long-term weight regain, suggesting its potential as a genetic biomarker for predicting differential responses to bariatric surgery.