JCEM:RYGB的减肥效果受多种遗传变异影响
2013-05-14 JCEM dxy
Roux-en-Y胃旁路术(RYGB)是极度肥胖和肥胖相关并发症最有效的治疗方法之一。然而,尽管有潜在的疗效,许多患者不能达到和/或维持充分的体重下降。为了确定在RYGB术后,减肥效果中遗传因素潜在的变异性,来自美国宾夕法尼亚大学医学院个体化治疗研究所的Harry Ostrer教授及其团队进行了一项研究,该研究发现RYGB术后,减肥效果的变化可能受数个常见的遗传变异影响。该研究结果在线发表在201
Roux-en-Y胃旁路术(RYGB)是极度肥胖和肥胖相关并发症最有效的治疗方法之一。然而,尽管有潜在的疗效,许多患者不能达到和/或维持充分的体重下降。为了确定在RYGB术后,减肥效果中遗传因素潜在的变异性,来自美国宾夕法尼亚大学医学院个体化治疗研究所的Harry Ostrer教授及其团队进行了一项研究,该研究发现RYGB术后,减肥效果的变化可能受数个常见的遗传变异影响。该研究结果在线发表在2013年4月30日的美国《临床内分泌代谢杂志》(The journal of clinical endocrinology & metabolism)上。
该研究运用2阶段极端表型研究设计进行一项全基因组相关研究。在一个综合医疗卫生系统的综合减肥计划中招募患者。86例伴有最低比例额外体重丢失(%EBWL)的肥胖患者(体重指数>35kg/m2)和89例伴有最高比例额外体重丢失的患者,在手术后2年使用昂飞公司6.0版本的单核苷酸多态性(SNP)序列进行基因分型。同一队列的第二个小组,包含164例下四分位数%EBWL患者和169例上四分位数%EBWL患者,被选出使用传统单核苷酸多态性序列评估候选区域。受试者进行RYGB手术干预,评估RYGB术后2年%EBWL和SNPs。
该研究结果表明,在第一阶段分析中确认了111SNPs,在体重下降的2个极端表型的频率有显著差异(等位基因X2检验P<0.0001)。手术后2年,%EBWL的线性回归显示17SNPs在校验阶段接近P<0.05,并聚集在或靠近具有潜在生物相关性的数个基因,包括PKHD1、HTR1A、NMBR和IGF1R。
该研究是第一个RYGB体重减轻反应的全基因组相关研究。RYGB术后,减肥效果的变化可能受数个常见的遗传变异影响。
与胃旁路术相关的拓展阅读:
- JCEM:Roux-en-Y胃旁路术术后胰岛素清除增加
- STM:胃旁路术的部分益处可能是肠道微生物变化的结果
- 胃旁路术可使轻度肥胖患者的糖尿病缓解
- 胃旁路术与胆胰转流术均能较好控制糖尿病大鼠血糖水平 更多信息请点击:有关胃旁路术更多威廉亚洲官网
Genome-wide Association of Single-Nucleotide Polymorphisms With Weight Loss Outcomes After Roux-en-Y Gastric Bypass Surgery.
Context
Roux-en-Y gastric bypass (RYGB) is among the most effective treatments for extreme obesity and obesity-related complications. However, despite its potential efficacy, many patients do not achieve and/or maintain sufficient weight loss.
Objective
Our objective was to identify genetic factors underlying the variability in weight loss outcomes after RYGB surgery.
Design
We conducted a genome-wide association study using a 2-stage phenotypic extreme study design.
Setting
Patients were recruited from a comprehensive weight loss program at an integrated health system.
Patients
Eighty-six obese (body mass index >35 kg/m2) patients who had the least percent excess body weight loss (%EBWL) and 89 patients who had the most %EBWL at 2 years after surgery were genotyped using Affymetrix version 6.0 single-nucleotide polymorphism (SNP) arrays. A second group from the same cohort consisting of 164 patients in the lower quartile of %EBWL and 169 from the upper quartile were selected for evaluation of candidate regions using custom SNP arrays.
Intervention
We performed RYGB surgery.
Main Outcome Measures
We assessed %EBWL at 2 years after RYGB and SNPs.
Results
We identified 111 SNPs in the first-stage analysis whose frequencies were significantly different between 2 phenotypic extremes of weight loss (allelic χ2 test P < .0001). Linear regression of %EBWL at 2 years after surgery revealed 17 SNPs that approach P < .05 in the validation stage and cluster in or near several genes with potential biological relevance including PKHD1, HTR1A, NMBR, and IGF1R.
Conclusions
This is the first genome-wide association study of weight loss response to RYGB. Variation in weight loss outcomes after RYGB may be influenced by several common genetic variants.
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