Bivariate linkage between acylation-stimulating protein and BMI and high-density lipoproteins.
OBJECTIVE
Given the importance of visceral adiposity in the metabolic syndrome, whether levels of adipokines have shared genetic effects (pleiotropy) with aspects of the metabolic syndrome should be addressed. Acylation-stimulating protein (ASP), an adipose-derived protein, influences lipid metabolism, obesity, and glucose use. Therefore, our objective was to examine the genetic regulation of ASP and associated pleiotropic effects.


METHODS
We assayed serum ASP levels in 435 Mexican Americans participating in the San Antonio Family Heart Study and performed univariate and bivariate variance components analysis.


RESULTS
Additive genetic heritability of ASP was 26% (p = 0.0004). Bivariate genetic analysis detected significant genetic correlations between ASP and several lipid measures but not between ASP and adiposity or diabetes measures. We detected two potential quantitative trait loci influencing ASP levels. The strongest signal was on chromosome 17 near marker D17S1303 [log of the odds ratio (LOD) = 2.7]. The signal on chromosome 15 reached its peak near marker D15S641 (LOD = 2.1). Both signals localize in regions reported to harbor quantitative trait loci influencing obesity and lipid phenotypes in this population. Bivariate linkage analysis yielded LODs of 4.7 for ASP and BMI on chromosome 17 and 3.2 for ASP and high-density lipoprotein2a on chromosome 15.


CONCLUSIONS
Given these findings, there seems to be a significant genetic contribution to variation in circulating levels of ASP and an interesting pattern of genetic correlation (i.e., pleiotropy) with other risk factors associated with the metabolic syndrome.
Martin
Lisa J
LJ
Southwest Foundation for Biomedical Research, San Antonio, Texas, USA. lisa.martin@cchmc.org
Cianflone
Katherine
K
Zakarian
Robert
R
Nagrani
Gauri
G
Almasy
Laura
L
Rainwater
David L
DL
Cole
Shelley
S
Hixson
James E
JE
MacCluer
Jean W
JW
Blangero
John
J
Comuzzie
Anthony G
AG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000235:genetics*; D015992:Body Mass Index; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D015926:Complement C3a / Q000031:analogs & derivatives*; D005260:Female; D008040:Genetic Linkage; D006630:Hispanic or Latino; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D008126:Lod Score; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D040641:Quantitative Trait Loci
D001798:Blood Proteins; D008075:Lipoproteins, HDL; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a