title: The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes.
abstract: BACKGROUND
  Ghrelin and its receptor play an important role in glucose metabolism and energy homeostasis, and therefore they are functional candidates for genes carrying susceptibility alleles for type 2 diabetes.
  
  
  METHODS
  We assessed common genetic variation of the ghrelin (GHRL; five single nucleotide polymorphisms (SNP)) and the ghrelin-receptor (GHSR) genes (four SNPs) in 610 Caucasian patients with type 2 diabetes and 820 controls. In addition, promoter reporter assays were conducted to model the regulatory regions of both genes.
  
  
  RESULTS
  Neither GHRL nor GHSR gene SNPs were associated with type 2 diabetes. One of the ghrelin haplotypes showed a marginal protective role in type 2 diabetes. We observed profound differences in the regulation of the GHRL gene according to promoter sequence variants. There are three different GHRL promoter haplotypes represented in the studied cohort causing up to 45% difference in the level of gene expression, while the promoter region of GHSR gene is primarily represented by a single haplotype.
  
  
  CONCLUSIONS
  The GHRL and GHSR gene variants are not associated with type 2 diabetes, although GHRL promoter variants have significantly different activities.
authors.affiliation: Department of Endocrinology, Barts and London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Garcia
authors.forename: Peter
authors.initials: P
authors.lastname: King
authors.forename: Kally
authors.initials: K
authors.lastname: Sidhu
authors.forename: Hideko
authors.initials: H
authors.lastname: Ohgusu
authors.forename: Andrew
authors.initials: A
authors.lastname: Walley
authors.forename: Cecile
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Maria
authors.initials: M
authors.lastname: Gueorguiev
authors.forename: Sahira
authors.initials: S
authors.lastname: Khalaf
authors.forename: Derek
authors.initials: D
authors.lastname: Davies
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
authors.forename: Phillipe
authors.initials: P
authors.lastname: Froguel
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D054439:Ghrelin / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051381:Rats; D054440:Receptors, Ghrelin / Q000235:genetics*; D014162:Transfection
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin; D004247:DNA