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Biliary lipid composition in heterozygous familial hypercholesterolemia and influence of treatment with probucol

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Abstract

The lipid composition of fasting duodenal bile was determined in 11 healthy subjects with normolipidemia and 15 patients with heterozygous familial hypercholesterolemia (FH) (12 with type IIa, three with type IIb). The age distribution among the groups of subjects was similar. In the patients with heterozygous FH type IIa, the mean value for molar percentage of cholesterol and lithogenic index (LI) of bile were significantly higher than those of controls (8.4±1.0%, 1.47±0.18 calculated by Hegard, Dam, and Holzbach vs 4.3±0.4%, 0.81±0.07, respectively). The value of LI in the patients with FH type IIb was also found to be significantly higher than that of the controls. In the patients with heterozygous FH type IIa, we observed both a significant decrease in the molar percentages of glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycolithocholic acid, and a significant increase of taurochenodeoxycholic acid compared to the corresponding values in the controls. Bile analysis of six patients was reexamined during probucol treatment after 16 weeks. Probucol significantly lowered serum cholesterol levels. However, biliary lipid composition and individual bile acid proportions was not altered by the treatment. The results suggest that most of the patients with heterozygous FH have supersaturated bile and are predisposed to cholesterol gallstone formation. In addition, the mechanism by which probucol lowers serum cholesterol appears to be independent of any change in the metabolism of biliary lipid.

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References

  1. Turley SD, Dietschy JD: Cholesterol metabolism and excretion.In The Liver: Biology and Pathobiology. I Arias, H Popper, D. Schachter, DA Shafritz (eds). New York, Raven Press, 1982, pp 467–492

    Google Scholar 

  2. Goldstein JL, Brown MS: Familial Hypercholesterolemia. The Metabolic Basis of Inherited Disease, 5th ed. New York, McGraw-Hill, 1983, pp 672–712

    Google Scholar 

  3. Goldstein JL, Kita T, Brown MS: Defective lipoprotein receptors and atherosclerosis; lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med 309:288–296, 1983

    Google Scholar 

  4. Attie AD, Pittman RC, Steinberg D: Hepatic catabolism of low density lipoprotein: Mechanisms and metabolic consequences. Hepatology 2:269–281, 1982

    Google Scholar 

  5. Mahley RW, Innerarity TL: Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta 737:197–222, 1983

    Google Scholar 

  6. Hellström K, Angelin B, Einarsson K, Kallmer M, Leijd B: Regulation of bile acid synthesis in hyperlipoproteinemia.In Bile Acid Metabolism in Health and Disease. G Paumgartner, A. Stiehl (ed). London, MTP Press, 1977, pp 235–239

    Google Scholar 

  7. Angelin B, Einarsson K, Hellström K, Leijd B: Bile acid kinetics in relation to endogenous triglyceride metabolism in various types of hyperlipoproteinemia. J Lipid Res 19:1004–1016, 1978

    Google Scholar 

  8. Ahlberg J, Angelin B, Einarsson K, Hellström K, Leijd B: Biliary lipid composition in normo- and hyperlipoproteinemia. Gastroenterology 79:90–94, 1980

    Google Scholar 

  9. Leiss O, Meyer-Krahmer K, von Bergmann K: Biliary lipid secretion in patients with heterozygous familial hypercholesterolemia and combined hyperlipidemia. Influence of bezafibrate and fenofibrate. J Lipid Res 27:713–723, 1986

    Google Scholar 

  10. Linden NH, Rooy FWM, Jansen H: Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolemia. Gut 31:348–350, 1990

    Google Scholar 

  11. Miettinen TA: Mode of action of a new hypocholesteraemic drug (DH-581) in familial hypercholesteraemia. Atherosclerosis 15:163–176, 1972

    Google Scholar 

  12. Strandberg T, Kuusi T, Tilvis R, Miettinen TA: Effect of probucol on cholesterol synthesis, plasma lipoproteins and the activities of lipoprotein and hepatic lipase in the rat. Atherosclerosis 40:193–201, 1981

    Google Scholar 

  13. Miettinen TA, Huttumen JK, Kuusi T, Kumlin T, Mattila S, Naukkarinen V, Strandberg T: Effect of probucol on the activity of postheparin plasma lipoprotein lipase and hepatic lipase. Clin Chim Acta 113:59–64, 1981

    Google Scholar 

  14. Kesaniemi YA, Grundy SM: Influence of probucol on cholesterol and lipoprotein metabolism in man. J Lipid Res 25:780–790, 1984

    Google Scholar 

  15. Richmond W: Preparation and properties of a cholesterol oxidase fromNocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 19:1350–1356, 1973

    Google Scholar 

  16. Bucolo G, David H. Quantitative determination of serum triglycerides by the use of enzyme. Clin Chem 19:476–482, 1973

    Google Scholar 

  17. Goto J, Kato H, Saruta Y, Nambara T: Separation and determination of bile acids in human bile by high performance liquid chromatography. J Liquid Chromatogr 3:991–1003, 1980

    Google Scholar 

  18. Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917, 1959

    Google Scholar 

  19. Ikuta S, Matuura K, Imamura S, Misaki H, Horiuti Y: Oxidative pathway of choline to betanine in the soluble fraction prepared fromArthrobacter globiformis. J Biochem 82:157–163, 1977

    Google Scholar 

  20. Thomas PJ, Hofmann AF: A simple calculation of the lithogenic index of bile; expressing biliary lipid composition on rectangular coordinates. Gastroenterology 65:698–700, 1973

    Google Scholar 

  21. Admirand WH, Small DM: The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest 47:1043–1052, 1968

    Google Scholar 

  22. Hegard FG, Dam H: The solubility of cholesterol in aqueous solutions of bile salts and lecithin. Z Ernaehrungswiss 10:223–233, 1971

    Google Scholar 

  23. Holzbalch RT, Marsh M, Olzewski M, Holan K: Cholesterol solubility in bile: evidence that supersaturated bile is frequent in healthy man. J Clin Invest 52:1467–1479, 1973

    Google Scholar 

  24. Bennion LJ, Grundy SM: Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest 56:996–1011, 1975

    Google Scholar 

  25. Small DM: Pathogenesis of cholesterol stones.In Bockus Gastroenterology, 4th ed. JE Berk (ed). Philadelphia, WB Saunders, 1985, pp 3499–3509

    Google Scholar 

  26. Mitchell JC, Stone BG, Logan GM, Duane WC: Role of cholesterol synthesis in regulation of bile acid synthesis and biliary cholesterol secretion in humans. J Lipid Res 32:1143–1149, 1991

    Google Scholar 

  27. Brown MS, Goldstein JL: Expression of the familial hypercholesterolemia gene in heterozygotes: Mechanisms for a dominant disorder in man. Science 185:61–63, 1974

    Google Scholar 

  28. Ho YK, Faust JR, Bilheimer DW, Brown MS, Goldstein JL: Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes. Comparison of cells from normal subjects and patients with homozygous familial hypercholesterolemia and abetalipoproteinemia. J Exp Med 145:1531–1549, 1977

    Google Scholar 

  29. Sjovall J. Bile acids in man under normal and pathological conditions. Bile acids and steroids. Clin Chim Acta 5:33–41, 1960

    Google Scholar 

  30. Schersten T: The synthesis of taurocholic and glycocholic acids by preparations of human liver, I. Distribution of activity between subcellular fractions. Biochim Biophys Acta 141:144–154, 1967

    Google Scholar 

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Authors and Affiliations

  1. Internal Medicine, Saiseikan Hospital, 990, Yamagata, Japan

    Naoaki Tanno MD, Shinichi Oikawa MD, Masaru Koizumi MD, Hidetoshi Kotake MD, Hidetoshi Hirakawa MD, Yoshihiko Kanazawa MD & Takayoshi Toyota MD

  2. Kanazawa Clinic, 980, Sendai, Japan

    Naoaki Tanno MD, Shinichi Oikawa MD, Masaru Koizumi MD, Hidetoshi Kotake MD, Hidetoshi Hirakawa MD, Yoshihiko Kanazawa MD & Takayoshi Toyota MD

  3. The Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryou-machi, Aobaku, 980, Sendai, Japan

    Naoaki Tanno MD, Shinichi Oikawa MD, Masaru Koizumi MD, Hidetoshi Kotake MD, Hidetoshi Hirakawa MD, Yoshihiko Kanazawa MD & Takayoshi Toyota MD

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  1. Naoaki Tanno MD
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  2. Shinichi Oikawa MD
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Tanno, N., Oikawa, S., Koizumi, M. et al. Biliary lipid composition in heterozygous familial hypercholesterolemia and influence of treatment with probucol. Digest Dis Sci 39, 1586–1591 (1994). https://doi.org/10.1007/BF02088069

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  • DOI: https://doi.org/10.1007/BF02088069

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