Genome-wide scan of plasma cholecystokinin in baboons shows linkage to human chromosome 17.
OBJECTIVE
Cholecystokinin (CCK) is known to inhibit food intake and is an important signal for controlling meal volume, indicating a possible role in weight regulation. Our objective was to investigate genetic influences on plasma CCK in baboons.


METHODS
Subjects were 376 baboons (males = 113, females = 263) from the Southwest National Primate Research Center, housed at the Southwest Foundation for Biomedical Research, San Antonio, Texas. Anthropometric and biochemical parameters were analyzed. Genetic effects on plasma CCK were estimated by the maximum likelihood-based variance components method implemented in the software program SOLAR (Sequential Oligogenic Linkage Analysis Routines).


RESULTS
Male baboons (32.7 +/- 6 kg) were much heavier than females (20.2 +/- 4 kg). Similarly, mean (+/- standard deviation) plasma CCK values were also higher in male baboons (13.8 +/- 6 pM) than female baboons (12.5 +/- 4 pM). Significant heritabilities were observed for plasma CCK (0.14 +/- 0.1, p < 0.05), body weight (h2 = 0.62 +/- 0.15, p < 10(-8)), and glucose (h2 = 0.68 +/- 0.17, p < 10(-7)). A genome-wide scan of plasma CCK detected a strong signal for a quantitative trait locus (QTL) on chromosome 17p12-13 [logarithm of the odds (LOD) = 3.1] near marker D17S804. Suggestive evidence of a second QTL was observed on chromosome 4q34-35 (LOD = 2.3) near marker D4S2374.


CONCLUSIONS
A substantial contribution of additive genetic effects to the variation in plasma levels of CCK was demonstrated in baboons. The identification of a QTL for plasma CCK on chromosome 17p is significant, as several obesity-related traits such as BMI, leptin, adiponectin, and acylation stimulating protein have already been mapped to this region.
Voruganti
V Saroja
VS
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA. svorugan@darwin.sfbr.org
Tejero
M Elizabeth
ME
Proffitt
J Michael
JM
Cole
Shelley A
SA
Freeland-Graves
Jeanne H
JH
Comuzzie
Anthony G
AG
D000818:Animals; D002766:Cholecystokinin / Q000097:blood / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D048529:Papio hamadryas / Q000097:blood / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics
D002766:Cholecystokinin