Secció de Zoologia i Antropologia Biòlogica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
Secció de Zoologia i Antropologia Biòlogica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Department of Biological Psychology, Vrije Universiteit, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, Netherlands.
Surg Obes Relat Dis. 2024 Sep;20(9):814-821. doi: 10.1016/j.soard.2024.04.002. Epub 2024 Apr 6.
Obesity is a polygenic multifactorial disease. Recent genome-wide association studies have identified several common loci associated with obesity-related phenotypes. Bariatric surgery (BS) is the most effective long-term treatment for patients with severe obesity. The huge variability in BS outcomes between patients suggests a moderating effect of several factors, including the genetic architecture of the patients.
To examine the role of a genetic risk score (GRS) based on 7 polymorphisms in 5 obesity-candidate genes (FTO, MC4R, SIRT1, LEP, and LEPR) on weight loss after BS.
University hospital in Spain.
We evaluated a cohort of 104 patients with severe obesity submitted to BS (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for >60 months (lost to follow-up, 19.23%). A GRS was calculated for each patient, considering the number of carried risk alleles for the analyzed genes. During the postoperative period, the percentage of excess weight loss total weight loss and changes in body mass index were evaluated. Generalized estimating equation models were used for the prospective analysis of the variation of these variables in relation to the GRS.
The longitudinal model showed a significant effect of the GRS on the percentage of excess weight loss (P = 1.5 × 10), percentage of total weight loss (P = 3.1 × 10), and change in body mass index (P = 7.8 × 10) over time. Individuals with a low GRS seemed to experience better outcomes at 24 and 60 months after surgery than those with a higher GRS.
The use of the GRS in considering the polygenic nature of obesity seems to be a useful tool to better understand the outcome of patients with obesity after BS.
肥胖是一种多基因、多因素疾病。最近的全基因组关联研究已经确定了几个与肥胖相关表型相关的常见基因座。减重手术（BS）是治疗严重肥胖患者最有效的长期治疗方法。患者之间 BS 结果的巨大差异表明，有几个因素起着调节作用，包括患者的遗传结构。
研究基于 5 个肥胖候选基因（FTO、MC4R、SIRT1、LEP 和 LEPR）中的 7 个多态性的遗传风险评分（GRS）对 BS 后体重减轻的作用。
西班牙大学医院。
我们评估了 104 例接受 BS（Roux-en-Y 胃旁路术或袖状胃切除术）的严重肥胖患者队列，随访时间超过 60 个月（失访率为 19.23%）。为每位患者计算了 GRS，考虑了分析基因中携带的风险等位基因数。在术后期间，评估了总体重减轻的多余体重减轻百分比和体重指数的变化。使用广义估计方程模型对这些变量与 GRS 的关系进行前瞻性分析。
纵向模型显示 GRS 对多余体重减轻百分比（P=1.5×10）、总体重减轻百分比（P=3.1×10）和体重指数变化（P=7.8×10）具有显著影响。在手术后 24 和 60 个月时，低 GRS 个体的结果似乎优于高 GRS 个体。
在考虑肥胖的多基因性质时使用 GRS 似乎是一种有用的工具，可以更好地理解 BS 后肥胖患者的结果。
