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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2729-2736.)
© 1997 American Heart Association, Inc.

Articles

Etiologic Heterogeneity of Hyperapobetalipoproteinemia (HyperapoB)

Results From Segregation Analysis in Families With Premature Coronary Artery Disease

Suh-Hang Hank Juo; Terri H. Beaty; ; Peter O. Kwiterovich, Jr

From the Department of Epidemiology, The Johns Hopkins School of Hygiene and Public Health (S.-H.H.J., T.H.B.), and the Department of Medicine and Pediatrics, The Johns Hopkins School of Medicine (P.O.K.), Baltimore, Md.

Abstract Hyperapobetalipoproteinemia (hyperapoB) is a common familial lipoprotein disorder associated with premature coronary artery disease (CAD). HyperapoB is characterized by an increased number of small, dense LDL particles. Patients with hyperapoB may be normotriglyceridemic (normoTG) or hypertriglyceridemic (hyperTG). We tested the hypothesis that a major locus controls the hyperapoB phenotype by using data from 1035 participants in 145 families enriched for premature CAD. Segregation analysis was conducted, and results suggest etiologic heterogeneity in these families. Families (n=55) with one or more hyperTG hyperapoB individuals strongly supported mendelian recessive inheritance of hyperapoB. Under this mendelian model, individuals with the high-risk genotype had a baseline risk of 0.78, but parental and spouse's hyperapoB phenotypes did influence the probability of displaying hyperapoB. Low-risk genotypes had virtually no risk of displaying hyperapoB. The other subgroup of families (n=72), in which all hyperapoB individuals were normoTG, did not show any clear pattern of inheritance. Eighteen families did not have any hyperapoB individual. In the 55 families with hyperTG hyperapoB, diabetes was more prevalent in hyperapoB individuals (18.3% of hyperTG hyperapoB individuals, 9.6% of normoTG hyperapoB individuals) than in normal individuals (4.9%). Both hyperTG hyperapoB and normoTG hyperapoB phenotypes were significant predictors for blood pressure in the 55 families, but not in the total population. These associations further suggest a link between hyperapoB and the small, dense LDL syndromes. This study successfully demonstrated mendelian inheritance of the hyperapoB phenotype and also suggested etiologic heterogeneity of hyperapoB.

Key Words: hyperapoB • apolipoprotein B • familial combined hyperlipidemia • coronary artery disease • segregation analysis • etiologic heterogeneity

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