© 1995 American Heart Association, Inc.
Articles |
A Major Locus Influencing Plasma High-Density Lipoprotein Cholesterol Levels in the San Antonio Family Heart Study
Segregation and Linkage Analyses
From the Department of Genetics, Southwest Foundation for Biomedical Research, and the Division of Epidemiology (M.P.S.), University of Texas Health Science Center at San Antonio, San Antonio, Tex.
Correspondence to Michael C. Mahaney, PhD, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 28147, San Antonio, TX 78228-0147. E-mail mmahaney@darwin.sfbr.org.
Abstract To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P<.05), apoB (P<.01), hepatic lipase (P<.001), lipoprotein lipase (P<.001), and the LDL receptor (P<.001). While not excluding the apoE locus (LOD=-0.348, P<.21), the analysis provided no support for tight linkage between it and the detected major locus.
Key Words: HDL cholesterol • inheritance • linkage • candidate genes • genetic epidemiology
This article has been cited by other articles:
 |
|
 |
|
  Q. Yang, C.-Q. Lai, L. Parnell, L. A. Cupples, X. Adiconis, Y. Zhu, P. W. F. Wilson, D. E. Housman, A. M. Shearman, R. B. D'Agostino, et al. Genome-wide linkage analyses and candidate gene fine mapping for HDL3 cholesterol: the Framingham Study J. Lipid Res., July 1, 2005; 46(7): 1416 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Sonnenberg, G. R. Krakower, L. J. Martin, M. Olivier, A. E. Kwitek, A. G. Comuzzie, J. Blangero, and A. H. Kissebah Genetic determinants of obesity-related lipid traits J. Lipid Res., April 1, 2004; 45(4): 610 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Austin, K. L. Edwards, S. A. Monks, K. M. Koprowicz, J. D. Brunzell, A. G. Motulsky, M. C. Mahaney, and J. E. Hixson Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia J. Lipid Res., November 1, 2003; 44(11): 2161 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. O. Stehman-Breen, D. Gillen, M. Steffes, D. R. Jacobs Jr., C. E. Lewis, C. I. Kiefe, and D. Siscovick Racial Differences in Early-Onset Renal Disease among Young Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2352 - 2357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Canizales-Quinteros, C. A. Aguilar-Salinas, E. Reyes-Rodriguez, L. Riba, M. Rodriguez-Torres, S. Ramirez-Jimenez, A. Huertas-Vazquez, V. Fragoso-Ontiveros, A. Zentella-Dehesa, J. L. Ventura-Gallegos, et al. Locus on Chromosome 6p Linked to Elevated HDL Cholesterol Serum Levels and to Protection Against Premature Atherosclerosis in a Kindred With Familial Hypercholesterolemia Circ. Res., March 21, 2003; 92(5): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Woll, N. Q. Hanson, and M. Y. Tsai Absence of ABCA1 Mutations in Individuals with Low Serum HDL-Cholesterol Clin. Chem., March 1, 2003; 49(3): 521 - 522. [Full Text] [PDF]
|
|
|
|
 |
|
 M.C. Mahaney, L. Almasy, D.L. Rainwater, J.L. VandeBerg, S.A. Cole, J.E. Hixson, J. Blangero, and J.W. MacCluer A Quantitative Trait Locus on Chromosome 16q Influences Variation in Plasma HDL-C Levels in Mexican Americans Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 339 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington, T. D. Howard, G. A. Hawkins, D. M. Reboussin, J. Xu, S. L. Zheng, K. B. Brosnihan, D. A. Meyers, and E. R. Bleecker Estrogen-Receptor Polymorphisms and Effects of Estrogen Replacement on High-Density Lipoprotein Cholesterol in Women with Coronary Disease N. Engl. J. Med., March 28, 2002; 346(13): 967 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Coon, M. F. Leppert, J. H. Eckfeldt, A. Oberman, R. H. Myers, J. M. Peacock, M. A. Province, P. N. Hopkins, and G. Heiss Genome-Wide Linkage Analysis of Lipids in the Hypertension Genetic Epidemiology Network (HyperGEN) Blood Pressure Study Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1969 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Peacock, D. K. Arnett, L. D. Atwood, R. H. Myers, H. Coon, S. S. Rich, M. A. Province, and G. Heiss Genome Scan for Quantitative Trait Loci Linked to High-Density Lipoprotein Cholesterol: The NHLBI Family Heart Study Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1823 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Imperatore, W. C. Knowler, D. J. Pettitt, S. Kobes, J. H. Fuller, P. H. Bennett, and R. L. Hanson A Locus Influencing Total Serum Cholesterol on Chromosome 19p : Results From an Autosomal Genomic Scan of Serum Lipid Concentrations in Pima Indians Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2651 - 2656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Edwards, M. C. Mahaney, A. G. Motulsky, and M. A. Austin Pleiotropic Genetic Effects on LDL Size, Plasma Triglyceride, and HDL Cholesterol in Families Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2456 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Haffner, R. D'Agostino Jr, D. Goff, B. Howard, A. Festa, M. F. Saad, and L. Mykkanen LDL Size in African Americans, Hispanics, and Non-Hispanic Whites : The Insulin Resistance Atherosclerosis Study Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2234 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Mahaney, J. Blangero, D. L. Rainwater, G. E. Mott, A. G. Comuzzie, J. W. MacCluer, and J. L. VandeBerg Pleiotropy and Genotype by Diet Interaction in a Baboon Model for Atherosclerosis : A Multivariate Quantitative Genetic Analysis of HDL Subfractions in Two Dietary Environments Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zambon, S. S. Deeb, J. E. Hokanson, B. G. Brown, and J. D. Brunzell Common Variants in the Promoter of the Hepatic Lipase Gene Are Associated With Lower Levels of Hepatic Lipase Activity, Buoyant LDL, and Higher HDL2 Cholesterol Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1723 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Eberhart, A. J. Mendez, and M. W. Freeman Decreased Cholesterol Efflux from Fibroblasts of a Patient without Tangier Disease, but with Markedly Reduced High Density Lipoprotein Cholesterol Levels J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 836 - 846. [Abstract] [Full Text]
|
|
|
|
|
|
D. L. Rainwater, B. D. Mitchell, M. C. Mahaney, and S. M. Haffner Genetic Relationship Between Measures of HDL Phenotypes and Insulin Concentrations Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3414 - 3419. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Guerra, J. Wang, S. M. Grundy, and J. C. Cohen A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol PNAS, April 29, 1997; 94(9): 4532 - 4537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Mitchell, C. M. Kammerer, J. Blangero, M. C. Mahaney, D. L. Rainwater, B. Dyke, J. E. Hixson, R. D. Henkel, R. M. Sharp, A. G. Comuzzie, et al. Genetic and Environmental Contributions to Cardiovascular Risk Factors in Mexican Americans: The San Antonio Family Heart Study Circulation, November 1, 1996; 94(9): 2159 - 2170. [Abstract] [Full Text]
|
|