TY - JOUR
T1 - Etiologic heterogeneity of hyperapobetalipoproteinemia (hyperapoB)
T2 - Results from segregation analysis in families with premature coronary artery disease
AU - Juo, Suh Hang Hank
AU - Beaty, Terri H.
AU - Kwiterovich, Peter O.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Apolipoprotein B
KW - Coronary artery disease
KW - Etiologic heterogeneity
KW - Familial combined hyperlipidemia
KW - HyperapoB
KW - Segregation analysis
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U2 - 10.1161/01.ATV.17.11.2729
DO - 10.1161/01.ATV.17.11.2729
M3 - Article
C2 - 9409249
AN - SCOPUS:0031459891
SN - 1079-5642
VL - 17
SP - 2729
EP - 2736
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 11
ER -