Characterization of Ghrelin in Pedigreed Baboons: Evidence for Heritability and Pleiotropy

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 (h2= 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.