Characterization of ghrelin in pedigreed baboons: evidence for heritability and pleiotropy

Obesity (Silver Spring). 2008 Apr;16(4):804-10. doi: 10.1038/oby.2007.107. Epub 2008 Jan 31.

Abstract

Background: Ghrelin is an orexigenic hormone that is produced primarily in the stomach, and stimulates food intake via its receptors situated in the hypothalamus.

Objective: The purpose of this study was to characterize baboon ghrelin cDNA and investigate the genetic influence on the variation in plasma ghrelin levels in baboons.

Methods and procedures: The sample consisted of 376 baboons (263 females, 113 males) from a pedigreed colony at the Southwest Foundation for Biomedical Research, San Antonio, Texas. Ghrelin cDNA was cloned by reverse-transcription polymerase chain reaction (RT-PCR) and sequenced. Real-time RT-PCR was performed to quantify mRNA from the collected tissues. Genetic contribution to plasma ghrelin was estimated using a variance components method implemented in SOLAR.

Results: The baboon coding region and predicted amino acid sequence for ghrelin showed 97 and 96% sequence identity with humans, respectively. Maximum expression of ghrelin mRNA was detected in hypothalamus and stomach. Mean +/- s.e. plasma levels of ghrelin were 3,406 +/- 99 pg/ml. A significant heritability was observed for plasma ghrelin (h(2)= 0.25, P < 0.001). A genome-wide scan revealed the evidence of suggestive linkage for a locus affecting plasma ghrelin on chromosome 9q22 (between markers D9S910 and D9S261, logarithm of the odds (LOD) score = 2.3). Significant genetic correlations (P < 0.001) among ghrelin, body weight, and leptin were observed.

Discussion: These results indicate a significant genetic component in the variation of plasma ghrelin in baboons and reveal a high degree of similarity between baboon and human ghrelin with respect to its cDNA and its correlation with other obesity traits.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA, Complementary
  • Energy Metabolism / genetics*
  • Female
  • Genetic Linkage
  • Genetic Variation*
  • Ghrelin / blood
  • Ghrelin / genetics*
  • Male
  • Molecular Sequence Data
  • Obesity / genetics*
  • Obesity / metabolism
  • Papio hamadryas / genetics*
  • Papio hamadryas / metabolism
  • Pedigree
  • Phenotype
  • RNA, Messenger / metabolism

Substances

  • DNA, Complementary
  • Ghrelin
  • RNA, Messenger