Arteriosclerosis and Thrombosis, Vol 14, 1258-1263, Copyright © 1994 by American Heart Association

ARTICLES

Response to HMG CoA reductase inhibitors in heterozygous familial hypercholesterolemia due to the 10-kb deletion ("French Canadian mutation") of the LDL receptor gene

L Karayan, S Qiu, C Betard, R Dufour, G Roederer, A Minnich, J Davignon and J Genest Jr
Cardiovascular Genetics Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.

The 10-kb deletion ("French Canadian mutation") of the low-density lipoprotein (LDL) receptor gene is the most common mutation causing familial hypercholesterolemia among subjects of French Canadian descent. In affected subjects, it results in a null allele of the LDL receptor gene and provides a unique opportunity to examine single- allele regulation of this gene in humans. We sought to ascertain the response of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in subjects with the French Canadian mutation of the LDL receptor gene and to correlate this response with biochemical variables and the haplotype of the nondeletion LDL receptor allele. The prevalence of non-responders to high doses of HMG CoA reductase inhibitors (defined as < 15% decrease in LDL cholesterol [LDL-C] from baseline values after dietary intervention) was ascertained in 105 patients heterozygous for the 10-kb deletion after excluding first- degree relatives and those on combined lipid-lowering therapy or other lipid-lowering agents. Lipoprotein cholesterol levels were examined after a diet period (30% calories as fat) and after receiving HMG CoA reductase inhibitors as mono-therapy for a minimum of 3 months. The mean reduction in total cholesterol was 45 +/- 23%, in LDL-C 33 +/- 15%, and in triglycerides 32 +/- 49% (all P < .005). There was a slight increase in high-density lipoprotein cholesterol of 8.5 +/- 18% (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				D. S. Christidis, E. N. Liberopoulos, A. I. Kakafika, G. A. Miltiadous, M. Cariolou, E. S. Ganotakis, D. P. Mikhailidis, and M. S. Elisaf The effect of apolipoprotein e polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate. Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2006; 11(3): 211 - 221. [Abstract] [PDF]

				P. C.N. Rensen, L. A.J.M. Sliedregt, P. J. van Santbrink, M. Ferns, H. N.J. Schifferstein, S. H. van Leeuwen, J. H.M. Souverijn, T. J.C. van Berkel, and E. A.L. Biessen Stimulation of Liver-Directed Cholesterol Flux in Mice by Novel N-Acetylgalactosamine-Terminated Glycolipids With High Affinity for the Asialoglycoprotein Receptor Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 169 - 175. [Abstract] [Full Text] [PDF]

				G.R. Thompson, F. O'Neill, and M. Seed Why some patients respond poorly to statins and how this might be remedied Eur. Heart J., February 1, 2002; 23(3): 200 - 206. [Full Text] [PDF]

				F. H. O'Neill, D. D. Patel, B. L. Knight, C. K. Y. Neuwirth, M. Bourbon, A. K. Soutar, G. W. Taylor, G. R. Thompson, and R. P. Naoumova Determinants of Variable Response to Statin Treatment in Patients With Refractory Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 832 - 837. [Abstract] [Full Text] [PDF]

				N. D. Vaziri, K. Liang, and J. S. Parks Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome Am J Physiol Renal Physiol, May 1, 2001; 280(5): F823 - F828. [Abstract] [Full Text] [PDF]