title: Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery.
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.
authors.affiliation: Obesity Institute, Geisinger Clinic, 100 N Academy Ave, Danville, PA 17822-2130, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Matzko
authors.forename: George
authors.initials: G
authors.lastname: Argyropoulos
authors.forename: G Craig
authors.initials: GC
authors.lastname: Wood
authors.forename: Xin
authors.initials: X
authors.lastname: Chu
authors.forename: Roger J M
authors.initials: RJ
authors.lastname: McCarter
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Still
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Gerhard
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005260:Female; D015390:Gastric Bypass; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011184:Postoperative Period; D057234:Preoperative Period; D011401:Promoter Regions, Genetic / Q000235:genetics; D054440:Receptors, Ghrelin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015431:Weight Loss
chemical_list: D006442:Glycated Hemoglobin; D054440:Receptors, Ghrelin; C517652:hemoglobin A1c protein, human