JCEM：RYGB的减肥效果受多种遗传变异影响

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
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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.