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Association of Ghrelin Receptor Promoter Polymorphisms with Weight Loss Following Roux-en-Y Gastric Bypass Surgery

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

The role of increased ghrelin levels in weight loss outcomes following RYGB surgery may be influenced by variation in the GHSR gene.

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Acknowledgments

This work was supported by funds from Geisinger Clinic, the Weis Center for Research, and the Geisinger Obesity Research Institute and grants DK072488 (GSG and CDS) and DK088231 (GSG) from the NIH. We thank Ms. Christina Manney for her assistance with sample collection, data management, and patient access, and Ms. Amanda Stayer for excellent technical assistance with the promoter SNP analyses and luciferase experiments. We gratefully acknowledge the extraordinary cooperation and support of the patients enrolled in the Geisinger Bariatric surgery program without which this study would not have been possible.

Conflict of Interest

Co-author Christopher Still received grant and consulting support from Ethicon-Endosurgery. All the other authors have declared to have no conflicts of interest.

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Authors and Affiliations

  1. Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA, 17822-2130, USA

    Michelle E. Matzko, George Argyropoulos, G. Craig Wood, Xin Chu, Christopher D. Still & Glenn S. Gerhard

  2. Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA

    Michelle E. Matzko & Roger J. M. McCarter

  3. Weis Center for Research, Geisinger Clinic, 100 N. Academy Ave., Danville, PA, 17822-2130, USA

    George Argyropoulos, Xin Chu & Glenn S. Gerhard

  4. Center for Health Research, Geisinger Clinic, Danville, PA, USA

    G. Craig Wood

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  1. Michelle E. Matzko
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  2. George Argyropoulos
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  3. G. Craig Wood
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  4. Xin Chu
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Correspondence to Glenn S. Gerhard.

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Matzko, M.E., Argyropoulos, G., Wood, G.C. et al. Association of Ghrelin Receptor Promoter Polymorphisms with Weight Loss Following Roux-en-Y Gastric Bypass Surgery. OBES SURG 22, 783–790 (2012). https://doi.org/10.1007/s11695-012-0631-2

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