Multilocus genetic determinants of LDL particle size in coronary artery disease families

Jerome I. Rotter, Xiangdong Bu, Rita M. Cantor, Craig H Warden, Jane Brown, Richard J. Gray, Patricia J. Blanche, Ronald M. Krauss, Aldons J. Lusis

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (i) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (ii) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P = .008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P = .06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P = .01) and the manganese superoxide dismutase locus (chromosome 6) (P = .001), thus indicating multilocus determination of this atherogenic trait.

Original languageEnglish (US)
Pages (from-to)585-594
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Genetics


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