胃旁路手术后的体重减轻与 15q26.1 上的一个变异有关。
Weight loss after gastric bypass is associated with a variant at 15q26.1.
机构信息
Obesity, Metabolism, and Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
Am J Hum Genet. 2013 May 2;92(5):827-34. doi: 10.1016/j.ajhg.2013.04.009.
Abstract
The amount of weight loss attained after Roux-en-Y gastric bypass (RYGB) surgery follows a wide and normal distribution, and recent evidence indicates that this weight loss is due to physiological, rather than mechanical, mechanisms. To identify potential genetic factors associated with weight loss after RYGB, we performed a genome-wide association study (GWAS) of 693 individuals undergoing RYGB and then replicated this analysis in an independent population of 327 individuals undergoing RYGB. We found that a 15q26.1 locus near ST8SIA2 and SLCO3A1 was significantly associated with weight loss after RYGB. Expression of ST8SIA2 in omental fat of these individuals at baseline was significantly associated with weight loss after RYGB. Gene expression analysis in RYGB and weight-matched, sham-operated (WMS) mice revealed that expression of St8sia2 and Slco3a1 was significantly altered in metabolically active tissues in RYGB-treated compared to WMS mice. These findings provide strong evidence for specific genetic influences on weight loss after RYGB and underscore the biological nature of the response to RYGB.
摘要
接受 Roux-en-Y 胃旁路（RYGB）手术后的减重量呈宽正态分布，最近的证据表明这种减重是由于生理而非机械机制所致。为了确定与 RYGB 术后减重相关的潜在遗传因素，我们对 693 名接受 RYGB 的个体进行了全基因组关联研究（GWAS），然后在接受 RYGB 的 327 名独立个体中复制了该分析。我们发现，ST8SIA2 和 SLCO3A1 附近的 15q26.1 位点与 RYGB 后的减重显著相关。这些个体基线时网膜脂肪中 ST8SIA2 的表达与 RYGB 后的减重显著相关。RYGB 和体重匹配的假手术（WMS）小鼠的基因表达分析表明，与 WMS 小鼠相比，RYGB 治疗的代谢活跃组织中 St8sia2 和 Slco3a1 的表达显著改变。这些发现为 RYGB 后体重减轻的特定遗传影响提供了强有力的证据，并强调了对 RYGB 反应的生物学性质。
相似文献
1
Weight loss after gastric bypass is associated with a variant at 15q26.1.胃旁路手术后的体重减轻与 15q26.1 上的一个变异有关。
Am J Hum Genet. 2013 May 2;92(5):827-34. doi: 10.1016/j.ajhg.2013.04.009.
2
A Genetic Risk Score Is Associated with Weight Loss Following Roux-en Y Gastric Bypass Surgery.遗传风险评分与Roux-en-Y胃旁路手术后的体重减轻相关。
Obes Surg. 2016 Sep;26(9):2183-2189. doi: 10.1007/s11695-016-2072-9.
3
Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery.全基因组关联研究单核苷酸多态性与 Roux-en-Y 胃旁路手术后体重减轻的关系。
J Clin Endocrinol Metab. 2013 Jun;98(6):E1131-6. doi: 10.1210/jc.2012-3421. Epub 2013 Apr 30.
4
Weight Loss Following Roux-en-Y Gastric Bypass Causally Implicated with Serum Levels of IL-22: A Mendelian Randomization and Phenome-Wide Association Study.Roux-en-Y胃旁路术后体重减轻与血清白细胞介素-22水平存在因果关系：一项孟德尔随机化和全表型关联研究。
Obesity (Silver Spring). 2021 Mar;29(3):610-615. doi: 10.1002/oby.23097. Epub 2021 Feb 2.
5
Urinary phenotyping indicates weight loss-independent metabolic effects of Roux-en-Y gastric bypass in mice.尿表型分析表明 Roux-en-Y 胃旁路手术在小鼠中具有体重减轻以外的代谢作用。
J Proteome Res. 2013 Mar 1;12(3):1245-53. doi: 10.1021/pr300909v. Epub 2013 Feb 11.
6
A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery.靠近LYPLAL1基因的一种基因变异与胃旁路手术后较低的饥饿感及体重减轻增加有关。
Scand J Gastroenterol. 2016 Sep;51(9):1050-5. doi: 10.3109/00365521.2016.1166519. Epub 2016 May 16.
7
Revision Roux-en-Y Gastric Bypass to Biliopancreatic Long-Limb Gastric Bypass for Inadequate Weight Response: Case Series and Analysis.因体重减轻效果不佳，将Roux-en-Y胃旁路手术翻修为胆胰长肢胃旁路手术：病例系列及分析
Obes Surg. 2017 Sep;27(9):2293-2302. doi: 10.1007/s11695-017-2658-x.
8
Genes and networks expressed in perioperative omental adipose tissue are correlated with weight loss from Roux-en-Y gastric bypass.围手术期网膜脂肪组织中表达的基因和网络与Roux-en-Y胃旁路术后体重减轻相关。
Int J Obes (Lond). 2008 Sep;32(9):1395-406. doi: 10.1038/ijo.2008.106. Epub 2008 Jul 22.
9
Farnesoid X receptor contributes to body weight-independent improvements in glycemic control after Roux-en-Y gastric bypass surgery in diet-induced obese mice.法尼酯X受体有助于饮食诱导肥胖小鼠行Roux-en-Y胃旁路手术后血糖控制的改善，且这种改善与体重无关。
Mol Metab. 2020 Jul;37:100980. doi: 10.1016/j.molmet.2020.100980. Epub 2020 Mar 19.
10
The Role of FTO and Vitamin D for the Weight Loss Effect of Roux-en-Y Gastric Bypass Surgery in Obese Patients.FTO和维生素D在肥胖患者 Roux-en-Y 胃旁路手术减肥效果中的作用
Obes Surg. 2015 Nov;25(11):2071-7. doi: 10.1007/s11695-015-1644-4.
引用本文的文献
1
Utilization of a precision medicine genetic and psychosocial approach in outcome assessment of bariatric weight loss surgery: a narrative review.精准医学的遗传和社会心理方法在减肥手术结局评估中的应用：一项叙述性综述。
Front Public Health. 2025 May 1;13:1516122. doi: 10.3389/fpubh.2025.1516122. eCollection 2025.
2
Effect of weight loss following Roux-en-Y gastric bypass on cancer risk: A Mendelian randomization study.Roux-en-Y胃旁路术后体重减轻对癌症风险的影响：一项孟德尔随机化研究。
Medicine (Baltimore). 2025 Jan 31;104(5):e41351. doi: 10.1097/MD.0000000000041351.
3
CETP and APOA2 polymorphisms are associated with weight loss and healthy eating behavior changes in response to digital lifestyle modifications.CETP 和 APOA2 多态性与数字生活方式改变后体重减轻和健康饮食行为改变相关。
Sci Rep. 2023 Dec 7;13(1):21615. doi: 10.1038/s41598-023-48823-w.
4
Genetic variant panel allows predicting both obesity risk, and efficacy of procedures and diet in weight loss.基因变异检测 panel 能够预测肥胖风险以及减肥手术和饮食的效果。
Front Nutr. 2023 Nov 16;10:1274662. doi: 10.3389/fnut.2023.1274662. eCollection 2023.
5
Parental Obesity Predisposition and Age of Onset Associate with Poor Response to Bariatric and Metabolic Surgery.父母肥胖倾向和发病年龄与减重和代谢手术的不良反应相关。
Obes Surg. 2023 May;33(5):1519-1527. doi: 10.1007/s11695-023-06499-1. Epub 2023 Mar 1.
6
A Systematic Review of Genetic Correlates of Weight Loss After Bariatric Surgery.减重手术后体重减轻的遗传相关性的系统评价。
Obes Surg. 2021 Oct;31(10):4612-4623. doi: 10.1007/s11695-021-05585-6. Epub 2021 Aug 9.
7
Mechanisms of Weight Loss After Obesity Surgery.肥胖症手术后体重减轻的机制。
Endocr Rev. 2022 Jan 12;43(1):19-34. doi: 10.1210/endrev/bnab022.
8
Differentially Expressed Genes and Enriched Signaling Pathways in the Adipose Tissue of Obese People.肥胖人群脂肪组织中差异表达基因及富集信号通路
Front Genet. 2021 May 19;12:620740. doi: 10.3389/fgene.2021.620740. eCollection 2021.
9
Genetic markers of abdominal obesity and weight loss after gastric bypass surgery.腹型肥胖的遗传标志物与胃旁路手术后的体重减轻
PLoS One. 2021 May 28;16(5):e0252525. doi: 10.1371/journal.pone.0252525. eCollection 2021.
10
Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study.利用基因组关联在精准数字减肥护理中的应用：队列研究。
J Med Internet Res. 2021 May 19;23(5):e25401. doi: 10.2196/25401.
本文引用的文献
1
Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26.鉴定唾液酸转移酶 8B 为 15q25-26 染色体上精神和心境障碍的普遍易感性基因。
PLoS One. 2012;7(5):e38172. doi: 10.1371/journal.pone.0038172. Epub 2012 May 31.
2
The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control.Roux-en-Y 胃旁路术后胆汁在促进体重减轻和改善血糖控制中的作用。
Endocrinology. 2012 Aug;153(8):3613-9. doi: 10.1210/en.2011-2145. Epub 2012 Jun 6.
3
Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery.肠旁路手术后体重减轻需要黑素皮质素 4 受体信号传导。
J Clin Endocrinol Metab. 2012 Jun;97(6):E1023-31. doi: 10.1210/jc.2011-3432. Epub 2012 Apr 6.
4
Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice.肥胖小鼠行 Roux-en-Y 胃旁路术后静息能量消耗和摄食能量成本增加。
Endocrinology. 2012 May;153(5):2234-44. doi: 10.1210/en.2011-2041. Epub 2012 Mar 13.
5
Heritability of the weight loss response to gastric bypass surgery.胃旁路手术减肥效果的遗传性。
J Clin Endocrinol Metab. 2011 Oct;96(10):E1630-3. doi: 10.1210/jc.2011-1130. Epub 2011 Aug 10.
6
Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.在一个小鼠 7 号染色体同源导入供体区域的 8 个基因中，有 4 个是候选肥胖基因。
Physiol Genomics. 2011 Sep 22;43(18):1049-55. doi: 10.1152/physiolgenomics.00134.2010. Epub 2011 Jul 5.
7
A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort.对病态肥胖队列的胃、肝和脂肪组织基因表达的遗传学调查。
Genome Res. 2011 Jul;21(7):1008-16. doi: 10.1101/gr.112821.110. Epub 2011 May 20.
8
Water permeability and characterization of aquaporin-11.水通透率及水通道蛋白-11 的特性分析。
J Struct Biol. 2011 May;174(2):315-20. doi: 10.1016/j.jsb.2011.01.003. Epub 2011 Jan 18.
9
Selective reduction in neural responses to high calorie foods following gastric bypass surgery.胃旁路手术后对高热量食物的神经反应选择性降低。
Ann Surg. 2011 Mar;253(3):502-7. doi: 10.1097/SLA.0b013e318203a289.
10
MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes.MaCH：利用序列和基因型数据来估计单倍型和未观测基因型。
Genet Epidemiol. 2010 Dec;34(8):816-34. doi: 10.1002/gepi.20533.
Zotero 插件