Monogenic Obesity Mutations Lead to Less Weight Loss After Bariatric Surgery: a 6-Year Follow-Up Study
Monogenic Obesity Mutations Lead to Less Weight Loss After Bariatric Surgery: a 6-Year Follow-Up Study
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单基因肥胖突变导致减肥手术后体重减轻较少：一项 6 年随访研究
DOI：
10.1007/s11695-018-03623-4
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发表时间：
2019-04-01
期刊：
影响因子：
2.9
通讯作者：
Hu, Cheng
中科院分区：
文献类型：
--
作者：
Li, Yangyang;Zhang, Hong;Hu, Cheng
目标减肥手术正在成为肥胖患者最有效的治疗选择。下丘脑弓状核在代谢稳态中发挥重要作用。然而，与喂养中心相关的突变对减肥手术后体重减轻的影响仍不清楚。我们的目的是通过全外显子组测序（WES）诊断单基因肥胖，并探讨单基因突变是否影响减肥手术的效果。方法我们收集了2011年3月至2017年6月在上海接受腹腔镜袖状胃切除术的15至55岁、BMI> 28 kg/m2的肥胖患者。收集术前和术后与体重减轻和代谢特征相关的数据，包括空腹血糖（FBG）、高密度脂蛋白（HDL）胆固醇、低密度脂蛋白（LDL）胆固醇和甘油三酯。使用全血样本中的基因组 DNA 对肥胖患者进行 WES。结果我们调查了 131 名肥胖成人中携带一种突变的比例高达 8.4%，然后评估了这些突变与体重减轻之间的关联。突变携带者在短期和长期内的体重减轻均较少。生存分析表明，突变携带者更难达到体重减轻 20% 的目标（Plog-rank= 0.001；Pbreslow< 0.001），并且通过 Cox 回归模型，差异仍然显着。两组术后空腹血糖、高密度脂蛋白胆固醇和甘油三酯水平均有改善，但两组之间存在显着差异。结论我们的数据表明，8.4%的肥胖病例是由基因改变引起的，突变对减肥手术的效果有负面影响。
ObjectivesBariatric surgery is emerging as the most effective treatment option for patients with obesity. Hypothalamic arcuate nucleus plays an important role in metabolic homeostasis. However, the influence of mutations related to the feeding center on weight loss after bariatric surgery is still unclear. We aimed to diagnose monogenic obesity by whole exome sequencing (WES) and explore whether monogenic mutations influence the effectiveness of bariatric surgery.MethodsWe collected obese patients aged 15 to 55 with a BMI > 28 kg/m2and who underwent laparoscopic sleeve gastrectomy from March 2011 to June 2017 in Shanghai. Data related to weight loss and metabolic characteristics preoperatively and postoperatively were collected, including fasting blood glucose (FBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. WES was performed in obese patients using genomic DNA from whole blood samples.ResultsWe investigated the proportion of 131 obese adults with one mutation as high as to 8.4% and then evaluated the association between these mutations and weight loss. Mutation carriers had less weight loss over both short-term and long-term periods. Survival analyses indicated it was harder to attain the goal of 20% weight loss for mutation carriers (Plog-rank= 0.001;Pbreslow< 0.001), and the difference remained significant with a Cox regression model. Improvement in FBG, HDL cholesterol, and triglyceride levels postoperatively was observed in both groups, while there were significant differences between the two groups.ConclusionsOur data indicated that 8.4% of obesity cases were caused by change in genetics, and mutations had negative effects on the efficacy of bariatric surgery.