TY - JOUR
T1 - Apolipoprotein A-I/C-III/A-IV gene cluster in familial combined hyperlipidemia: Effects on LDL-cholesterol and apolipoproteins B and C-III
AU - Dallinga-Thie, G. M.
AU - Bu, X. D.
AU - van Linde-Sibenius Trip, M.
AU - Rotter, J. I.
AU - Lusis, A. J.
AU - de Bruin, T. W.
PY - 1996
Y1 - 1996
N2 - The underlying generic abnormalities in familial combined hyperlipidemia (FCH) hale not been elucidated, although previous association and linkage studies hale implicated the apoA-I/C-III/A-IV gene cluster. We now report studies of this cluster in 18 probands, 390 family members (hyperlipidemic relatives, n = 179; normolipidemic relatives, n = 211), and 177 spouses. Three restriction enzyme polymorphisms, XmnI and MspI sites 5' of the apoA-I gene and the SstI site in the 3' untranslated region of exon 4 of the apoC-III gene, were examined. In hyperlipidemic relatives and FCH probands, the frequency of each minor allele was significantly higher than in spouses. Associated with the higher frequency of minor alleles were elevated plasma cholesterol, triglycerides, LDL-cholesterol, apoB. and apoC-III levels. Quantitative sib-pair analysis revealed linkage between the MspI minor allele and plasma LDL cholesterol levels (P <0.04). The present data indicate that, while apoA-I/C-III/A-IV gene cluster is nor the primary cause of FCH, this cluster has a specific modifying effect on plasma triglyceride and LDL cholesterol levels
AB - The underlying generic abnormalities in familial combined hyperlipidemia (FCH) hale not been elucidated, although previous association and linkage studies hale implicated the apoA-I/C-III/A-IV gene cluster. We now report studies of this cluster in 18 probands, 390 family members (hyperlipidemic relatives, n = 179; normolipidemic relatives, n = 211), and 177 spouses. Three restriction enzyme polymorphisms, XmnI and MspI sites 5' of the apoA-I gene and the SstI site in the 3' untranslated region of exon 4 of the apoC-III gene, were examined. In hyperlipidemic relatives and FCH probands, the frequency of each minor allele was significantly higher than in spouses. Associated with the higher frequency of minor alleles were elevated plasma cholesterol, triglycerides, LDL-cholesterol, apoB. and apoC-III levels. Quantitative sib-pair analysis revealed linkage between the MspI minor allele and plasma LDL cholesterol levels (P <0.04). The present data indicate that, while apoA-I/C-III/A-IV gene cluster is nor the primary cause of FCH, this cluster has a specific modifying effect on plasma triglyceride and LDL cholesterol levels
M3 - Article
C2 - 8820109
SN - 0022-2275
VL - 37
SP - 136
EP - 147
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 1
ER -