SAT-705 The Prevalence of Mutations in the MC4R, POMC, and LEPR Genes in Thai Patients with Morbid Obesity Receiving Bariatric Surgery and Bariatric Surgery Outcomes

Abstract Disclosure: P. Greeviroj: None. T. Snabboon: None. N. Houngham: None. P. Santisitthanon: None. P. Boonchaya-anant: None. Background: Single gene disruptions within leptin-melanocortin pathway can cause severe early-onset obesity, known as monogenic obesity. The most common mutation is MC4R, followed by POMC and LEPR. The prevalence of these mutations in Thai bariatric surgery patients is still unknown. Methods: Data were collected from patients aged 18-70 with a BMI exceeding 30 kg/m2 who underwent bariatric surgery between 2011 and 2023. Sanger sequencing was performed on the MC4R, POMC, and LEPR genes. Mutation prediction software programs, including SIFT, PolyPhen-2, and MutationTaster, were used to assess the potential impact of novel mutations and variants of uncertain significance (VUS). After surgery, patients had follow-ups at 3, 6, 12, 18, and 24 months, and then annually. The primary outcome was the prevalence of mutations. Secondary outcomes were the differences in weight loss and diabetes remission post-bariatric surgery between mutation carriers and non-carriers. Results: Among 220 patients, 3 (1.4%) discovered new MC4R mutations: 1 with a missense mutation (c.904T>C) and 2 with frameshift mutations (c.597_599delCAT). Five patients (2.3%) had new LEPR mutations, including 6 missense mutations (c.77A>G, c.593T>A, c.707A>G, c.1936T>C, c.2059T>C, and c.3281A>G) and 1 splice donor variant (c.1912+2T>C). Variants of uncertain significance (VUS) in MC4R, POMC, and LEPR genes were found in 9 (4.1%), 9 (4.1%), and 18 (8.2%) patients, respectively. The prevalence of suspected pathogenic mutations predicted by mutation predictor programs was 0.45% in the MC4R gene, 0.9% in the POMC gene, and 1.8% in the LEPR gene. No previously reported pathogenic mutations were identified. There was no significant difference in weight loss and diabetes remission post-bariatric surgery between mutation carriers and non-carriers. Conclusion:MC4R, POMC, and LEPR mutations were rare in Thai patients with morbid obesity undergoing bariatric surgery. New mutations and VUS in these genes did not impact the effectiveness of bariatric surgery. Keyword: Obesity, Bariatric surgery, Obesity genetics, MC4R, POMC, LEPR, Remission of diabetes Presentation: Saturday, July 12, 2025