Association of Ghrelin Receptor Promoter Polymorphisms with Weight Loss Following Roux-en-Y Gastric Bypass Surgery
Association of Ghrelin Receptor Promoter Polymorphisms with Weight Loss Following Roux-en-Y Gastric Bypass Surgery
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DOI：
10.1007/s11695-012-0631-2
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发表时间：
2012-05-01
期刊：
影响因子：
2.9
通讯作者：
Gerhard, Glenn S.
中科院分区：
文献类型：
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作者：
Matzko, Michelle E.;Argyropoulos, George;Gerhard, Glenn S.
胃饥饿素在食欲中发挥作用，并被假设在Roux-en-Y胃旁路手术（RYGB）的机制中发挥作用。其受体基因启动子区域的单核苷酸多态性（snp）（生长激素促分泌素受体1a-GHSR型）也与糖耐量受损的成人长期饮食干预后的体重减轻结果有关。我们的目的是评估血清ghrelin水平的变化，并确定GHSR启动子多态性对rygb手术后体重减轻的影响。对37例接受RYGB手术的极度肥胖患者进行术前和术后6个月血清胃饥饿素水平测定。术中收集的肝组织中也测量了总胃饥饿素。对650多例RYGB患者进行了GHSR基因启动子区snp rs9819506和rs490683基因型与术后30个月体重减轻结果的相关性分析。RYGB手术后血清生长素水平升高。使用两种胃饥饿素snp的加性模型，体重减轻轨迹显著不同，rs490683 CC基因型纯合子的患者体重减轻最多。使用主导模型时，减肥轨迹也不同。rs490683风险等位基因在体外表现出启动子活性降低。胃促生长素水平升高在RYGB手术后减肥结果中的作用可能受到GHSR基因变异的影响。
Ghrelin plays a role in appetite and has been hypothesized to play a role in the mechanism of Roux-en-Y gastric bypass (RYGB) surgery. Single nucleotide polymorphisms (SNPs) in the promoter region of its receptor gene (growth hormone secretagogue receptor type 1a-GHSR) have also been associated with weight loss outcomes following long-term dietary intervention in adults with impaired glucose tolerance. Our objectives were to evaluate changes in serum ghrelin levels and determine the effect of GHSR promoter polymorphisms on post-RYGB surgery weight loss.Preoperative and 6-month postoperative serum ghrelin levels were measured in 37 patients with extreme obesity undergoing RYGB surgery. Total ghrelin was also measured in liver tissue collected intraoperatively. Association analysis between genotypes for SNPs rs9819506 and rs490683 in the promoter region of the GHSR gene and weight loss outcomes in the 30 months following surgery was performed in over 650 RYGB patients.Serum ghrelin levels increased after RYGB surgery. Weight loss trajectories were significantly different using an additive model for both ghrelin SNPs, with patients homozygous for the rs490683 CC genotype exhibiting the most weight loss. Weight loss trajectories were also different using a dominant model. The rs490683 risk allele demonstrated decreased promoter activity in vitro.The role of increased ghrelin levels in weight loss outcomes following RYGB surgery may be influenced by variation in the GHSR gene.