Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype
- Univ. of California, Los Angeles, CA (United States)
- Cedars-Sinai Research Inst., Los Angeles, CA (United States)
- University Hospital, Utrecht (Netherlands). Dept. of Medicine
- Lawrence Berkeley Lab., CA (United States)
Small, dense LDL particles consistently have been associated with hypertriglyceridemia, premature coronary artery disease (CAD), and familial combined hyperlipidemia (FCH). Previously, the authors have observed linkage of LDL particle size with four separate candidate-gene loci in a study of families enriched for CAD. These loci contain the genes for manganese superoxide dismutase (MnSOD), on chromosome 6q; for apolipoprotein AI-CIII-AIV, on chromosome 11q; for cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl-transferase (LCAT), on chromosome 16q; and for the LDL receptor (LDLR), on chromosome 19p. The authors have now tested whether these loci also contribute to LDL particle size in families ascertained for FCH. The members of 18 families (481 individuals) were typed for genetic markers at the four loci, and linkage to LDL particle size was assessed by nonparametric sib-pair linkage analysis. The presence of small, dense LDL (pattern B) was much more frequent in the FCH probands than in the spouse controls. Evidence for linkage was observed at the MnSOD (P = .02), CETP/LCAT (P = .03), and apolipoprotein AI0CIII0AIV loci (P = .005) but not at the LDLR locus. The authors conclude that there is a genetically based association between FCH and small, dense LDL and that the genetic determinants for LDL particle size are shared, at least in part, among FCH families and the more general population at risk for CAD.
- Sponsoring Organization:
- National Insts. of Health, Bethesda, MD (United States); USDOE, Washington, DC (United States)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 659010
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 63; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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