Title
Similar response to simvastatin in patients heterozygous for familial hypercholesterolemia with mRNA negative and mRNA positive mutations
Author
Sijbrands, E.J.G.
Lombardi, M.P.
Westendorp, R.G.J.
Gevers Leuven, J.A.
Meinders, A.E.
van der Laarse, A.
Frants, R.R.
Havekes, L.M.
Smelt, A.H.M.
Gaubius Instituut TNO
Publication year
1998
Abstract
In patients heterozygous for familial hypercholesterolemia, the low- density lipoprotein (LDL) cholesterol lowering effect of β-hydroxy-β- methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks, between heterozygous carriers of functionally different classes of mutations, i.e. mRNA negative or mRNA positive mutations. Out of 116 consecutive, unrelated patients with familial hypercholesterolemia, 27 patients were selected for molecular analyses: 14 patients with mRNA negative and 13 with mRNA positive mutations. Before simvastatin treatment, patients with mRNA negative mutations had higher levels of LDL cholesterol, lower levels of high-density lipoprotein (HDL) cholesterol and significantly more often tendon xanthomas, compared to patients with mRNA positive mutations. Simvastatin reduced the mean fasting LDL cholesterol levels to a similar percentage in the mRNA negative and mRNA positive patients (37, 36%, respectively, 95% CI of difference - 8 to 5%, P = 0.2). This effect was similar to the 37% decrease observed in our total series of patients with familial hypercholesterolemia (n = 116). The increase in mean concentration of HDL cholesterol was greater in the mRNA negative group than in the mRNA positive group (16, 0%, respectively, 95% CI of difference 8-25%, P = 0.002) independent of the response of total triglycerides to simvastatin. The percentage LDL cholesterol lowering response varied among multiple carriers of the same mutation, even in the case of mRNA negative mutations. We conclude that the percentage LDL lowering response to simvastatin treatment was similar in patients with mRNA negative and mRNA positive mutations. Moreover, variation of this response within multiple carriers of the same mutation suggests an influence of additional factors.
Subject
Health
Familial hypercholesterolemia
LDL receptor gene
Simvastatin
Xanthomas
Anticholesteremic Agents
Cholesterol, HDL
Cholesterol, LDL
Female
Heterozygote
Humans
Hyperlipoproteinemia Type II
Male
Middle Aged
Mutation
Receptors, LDL
RNA, Messenger
Simvastatin
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DOI
https://doi.org/10.1016/s0021-9150(97)00216-5
TNO identifier
234354
ISSN
0021-9150
Source
Atherosclerosis, 136 (2), 247-254
Document type
article