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The Journal of Lipid Research, Vol. 39, 437-441, February 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

The Ser447–Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins

James A. Thorna, Edward W. A. Needhamb,c, Raj K. Mattub,c, Joseph Stocksa, and David J. Galtona
a Department of Human Genetics and Metabolism, St. Bartholomew's Hospital, London, UK
b Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK
c Department of Biological Sciences, University of Warwick, Coventry, UK

Correspondence to: James A. Thorn.

Studies on monozygotic twins support a role for genetic determinants of plasma lipid, lipoprotein, and apolipoprotein levels. Gene variants of the enzyme lipoprotein lipase have been shown to associate with dyslipidemia and coronary artery disease. We assessed the gene–environment interaction by investigating the relationship between the lipoprotein lipase gene and plasma lipid, lipoprotein, and apolipoprotein variability and levels among 54 male monozygotic twin pairs (aged 18–28 years). The Ser447–Ter mutation (C->G transversion) was associated with significantly smaller within-pair differences in plasma high density lipoprotein-cholesterol (CG [n = 10] vs. CC [n = 44], 3.7 ± 5.3 mg/dl vs. 6.4 ± 5.2 mg/dl, P < 0.03) and total cholesterol (CG [n = 10] vs. CC [n = 44], 7.9 ± 9.4 mg/dl vs. 15.8 ± 12.7 mg/dl, P < 0.05), indicating attenuated variability in response to environmental stimuli.

This observation of a restrictive variability gene effect further supports a role for the lipoprotein lipase gene in the genetic regulation of lipids and lipoproteins and suggests that the Ser447–Ter mutation exerts multiple effects. This study also raises the possibility of a genetically determined responsiveness to dyslipidemia therapies.—Thorn, J. A., E. W. A. Needham, R. K. Mattu, J. Stocks, and D. J. Galton. The Ser447–Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins. J. Lipid Res. 1998. 39: 437–441.

Supplementary key words: lipoprotein lipase, LPL, exon 9 mutation, MZ twins, lipid/lipoprotein levels, variability gene, HDL-C


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