Lipoprotein Lipase Gene Variants and Coronary Risk
To the Editor:
In their paper concerning the Ser447-Stop substitution in the lipoprotein (Lp) lipase gene, Groenemeijer et al1 quoted only 2 publications by other groups when reporting associations of this mutation with lipid levels. When introducing their work, the authors stated that no studies had been reported in any substantial sample of subjects with angiographically defined coronary artery disease. We would like to recall our results published in 1995 from the ECTIM multicentric study including >600 patients with myocardial infarction and 700 matched controls.2 The Stop447 allele had a lowering effect on triglycerides (P<0.01) and apolipoprotein C-III (apoC-III) levels (P<0.001). These effects were consistently observed in the 4 populations included in the study (Belfast in Northern Ireland; Lille, Strasbourg, and Toulouse in France). The Stop447 allele was also associated with lower VLDL cholesterol (P<0.05), Lp E:B (P<0.01), and Lp C-III:B (P<0.05) levels and higher apoA-I levels (P<0.05). The Stop447 allele was weakly associated with a lower risk for myocardial infarction (odds ratio [CI]=0.81 [0.63 to 1.03], P=0.09, assuming a codominant model). A coronary angiogram was available for 412 French patients, and a coronary score was defined as the number of coronary arteries with >50% occlusion (range, 0 to 3). This score was not associated with the Ser447-Stop polymorphism. Although the rationale that led Groenemeijer et al1 to test the hypothesis of an interaction between β-blockers and the Ser447-Stop polymorphism was not evident to us, we reexamined our data to see if we could confirm this interaction. HDL cholesterol levels (mmol/L) were as follows (mean±SD): Stop447 absent, 1.20±0.33 (n=213) and 1.10±0.28 (n=295), no β-blockers versus with β-blockers; and Stop447 present, 1.15±0.34 (n=53) and 1.13±0.24 (n=67), no β-blockers versus with β-blockers, respectively. β-Blocker use lowered HDL cholesterol (P<0.001), but no interaction between β-blockers and the Ser447-Stop polymorphism was observed on HDL cholesterol. In β-blocker users, the increase in HDL cholesterol was marginal and not significant.
- Copyright © 1998 by American Heart Association
Groenemeijer BE, Hallman MD, Reymer PWA, Gagné E, Kuivenhoven JA, Bruin T, Jansen H, Lie KI, Bruschke AVG, Boerwinkle E, Hayden MR, Kastelein JJP. Genetic variant showing a positive interaction with β-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients: the Ser447-Stop substitution in the lipoprotein lipase gene. Circulation. 1997;95:2628–2635.
Jemaa R, Fumeron F, Poirier O, Lecerf L, Evans A, Arveiler D, Luc G, Cambou JP, Bard JM, Fruchart JC, Apfelbaum M, Cambien F, Tiret L. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels: the ECTIM study. J Lipid Res. 1995;36:2141–2146.