March 2012

Building on the legacy of a lipid pioneer

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The lipid community lost a pioneer, scientist, clinician and beloved teacher late last year. Tatu Miettinen passed away in November at the age of 81 in a car accident. Two papers published in 1965, the very early days of the Journal of Lipid Research, that Miettinen co-authored, “Quantitative isolation and gas-liquid chromatographic analysis of total fecal bile acids” and “Quantitative isolation and gas-liquid chromatographic analysis of total dietary and fecal neutral steroids,” are considered part of the groundwork of today’s understanding of cholesterol metabolism (1, 2).

Unbeknownst to many, Miettinen’s innovative thinking led to the development of the globally available product Benecol, a margarine product containing plant stanol ester, which has been shown to lower blood cholesterol levels. Miettinen was one of the founders of the 1990s research initiative the Scandinavian Simvastatin Survival Study, commonly known as 4S, which is considered a major milestone in cardiology research, as it provided clear evidence that statins reduce the risk of death by coronary heart disease. You can read more about Miettinen’s life and scientific legacy in “In Memoriam: Tatu A. Miettinen (1930 – 2011),” co-written by Y. Antero Kesaniemi of the University of Oulu and Oulu University Hospital and Scott M. Grundy of the University of Texas-Southwestern Medical Center at Dallas, published in the March issue of the JLR (doi:10.1194/jlr.E023853).

The apolipoprotein C-III research conducted by Ariel Brautbar of the Baylor College of Medicine and colleagues could be taken as an extension of Miettinen’s work, because without the positive results of 4S, other later statin studies would not have been possible. Increased apoC-III levels have been associated with atherosclerosis in both human and animal models. In “LPL gene variants affect apoC-III response to combination therapy of statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia” (doi:10.1194/jlr.M20404), trial participants took either fibrate (a medication that has been shown to increase HDL levels and decrease triglyceride levels) alone or in conjunction with a statin. Genetic variation via single polymorphisms was assessed in these individuals to determine if genetic differences had the expected positive effects on lipid and apolipoprotein levels by statin-fibrate combination therapy.

In total, three SNPs were identified in the lipoprotein lipase gene that increase apoC-III levels or seem to counteract the reduction in apoC-III levels usually seen with statin-fibrate combination therapy. While these SNPs were considered rare in frequency among the trial participants, all of whom had an increased risk for developing cardiovascular disease, this study represents the first report of genetic variation in the LPL gene region. Overall, Brautbar et al.’s findings suggest that the benefit of combination therapy may vary from individual to individual and that clinicians may need to tailor treatment regimens.
 

References
  1. 1. Grundy, Scott M., E.H. Ahrens, Jr., and Miettinen, T.A. (1965) Quantitative isolation and gas-liquid chromatographic analysis of total fecal bile acids. J. Lipid Res. 6, 397 – 410.
  2. 2. Miettinen, T.A., E.H. Ahrens, Jr., and Scott M. Grundy. (1965) Quantitative isolation and gas-liquid chromatographic analysis of total dietary and fecal neutral steroids. J. Lipid Res. 6, 411 – 424.

Mary L. Chang (mchang@asbmb.org) is managing editor of the JLR and coordinating journal manager of MCP.


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