ESR1, FTO, and UCP2 genes interact with bariatric surgery affecting weight loss and glycemic control in severely obese patients

Background: Significant variability in weight loss and glycemic control has been observed in obese patients receiving bariatric surgery. Genetic factors may play a role in the different outcomes. Methods: Five hundred and twenty severely obese patients with body mass index (BMI) ≥35 were recruited. Among them, 149 and 371 subjects received laparoscopic adjustable gastric banding (LAGB) and laparoscopic mini-gastric bypass (LMGB), respectively. All individuals were genotyped for five obesity-related single nucleotide polymorphisms on ESR1, FTO, PPARγ, and UCP2 genes to explore how these genes affect weight loss and glycemic control after bariatric surgery at the 6th month. Results: Obese patients with risk genotypes on rs660339-UCP2 had greater decrease in BMI after LAGB compared to patients with non-risk genotypes (-7.5 vs. -6 U, p=0.02). In contrast, after LMGB, obese patients with risk genotypes on either rs712221-ESR1 or rs9939609-FTO had significant decreases in BMI (risk vs. non-risk genotype, -12.5 vs. -10.0 U on rs712221, p=0.02 and -12.1 vs. -10.6 U on rs9939609, p=0.04) and a significant amelioration in HbA1c levels (p=0.038 for rs712221 and p<0.0001 for rs9939609). The synergic effect of ESR1 and FTO genes on HbA1c amelioration was greater (-1.54%, p for trend <0.001) than any of these genes alone in obese patients receiving LMGB. Conclusions: The genetic variants in the ESR, FTO, and UCP2 genes may be considered as a screening tool prior to bariatric surgery to help clinicians predict weight loss or glycemic control outcomes for severely obese patients.