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Clinical analysis of familial hypercholesterolemia, and establishing its gudeline

Familial hypercholesterolemia (FH) is a common genetic disease, incidence of which may be 1/200-500. The patients of FH show hypercholesterolemia, cutaneous and tendinous xanthomas, and coronary artery disease due to premature atherosclerosis.

FH patients are known to have mutation in LDL receptor gene which is known to function in incorporating LDL into the cells. Recently, mutations of other genes including LDLRAP1 and PCSK9 have been reported to be involved in the function of LDL receptor, and cause hypercholesterolemia. In our laboratory, 14 homozygous and 350 heterozygous FH patients have been followed and are subjected to analyze the risk for cardiovascular diseases. We have made guidelines for management of FH based on our data and reported to the Ministry of Health, Labor and Welfare.


  1. Teramoto T, Sasaki J, Harada-Shiba M, Arai H, Ishibasi S, Birou S, Bujo H, Daida H, Dohi S, Egusa G, Hiro T, Hirobe K, Iida M, Kihara S, Kinoshita M, Maruyama C, Nohara A, Ohta T, Oikawa S, Okada T, Okamura T, Watatsuki A, Yamashita S, Yokode M, YOkote K: Familial hypercholesterolemia, Executive summary of the Japan Atherosclerosis Society(JAS) Guidelines for diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan-2012 version, J Atheroscler Thromb, in press
  2. Yokoyama S, Ueshima H, Miida T, Nakamura M, Takata K, Fukukawa T, Goto T, Harada-Shiba M, Sano M, Kato K, Matsuda K: High-density lipoprotein of Japanese has markedly increased over the past twenty years, J Atheroscler Thromb, in press
  3. Harada-Shiba M, Arai H, Oikawa S, Ohta T, Okada T, Okamura T, Nohara A, Bujo H, Yokote K, Wakatsuki A, Ishibashi S, Yamashita S: Guidelines for the management of familial hypercholesterolemia: J Atheroscler Thromb, 2012; 19(12): 1043-1060.
  4. Harada-Shiba M, Arai H, Okamura T, Yokote K, Oikawa S, Nohara A, Okada T, Ohta T, Bujo H, Watanabe M, Wakatsuki A, Yamashita S: Multicenter study to determine the diagnosis criteria of heterozygous familial hypercholesterolemia in Japan: J Atheroscler Thromb, 2012; 19(11): 1019-1026.
  5. Sugisawa T, Okamura T, Makino H, Watanabe M, Kishimoto I, Miyamoto Y, Iwamoto N, Yamamoto A, Yokoyama S, Harada-Shiba M: Defining patients at extremely high risk for coronary artery disease in heterozygous familial hypercholesterolemia. J Atheroscler Thromb, 2012; 19(4) : 369-375.
  6. Yokoyama S, Yamashita S, Ishibashi S, Sone H, Oikawa S, Shirai K, Ohta T, Bujo H, Kobayashi J, Arai H, Harada-Shiba M, Eto M, Hayashi T, Gotoda T, Suzuki H, Yamada N: Background to discuss guidelines for control of plasma HDL-cholesterol in Japan. J Atheroscler Thromb, 2012; 19(3): 207-212.
  7. Gotoda T, Shirai K, Ohta T, Kobayashi J, Yokoyama S, Oikawa S, Bujo H, Ishibashi S, Arai H, Yamashita S, Harada-Shiba M, Eto M, Hayashi T, Sone H, Suzuki H, Yamada N: Diagnosis and management of type Ⅰ and type V hyperlipoproteinemia. J Atheroscler Thromb, 2012; 19: 1-12.
  8. Arai H, Ishibashi S, Bujo H, Hayashi T, Yokoyama S, Oikawa S, Kobayashi J, Shirai K, Ota T, Yamashita S, Gotoda T, Harada-Shiba M, Sone H, Eto M, Suzuki H, Yamada N: Management of type IIb dyslipidemia. J Atheroscler Thromb, 2012; 19: 105-114.
  9. Harada-Shiba M, Sugisawa T, Makino H, Abe M, Tsushima M, Yoshimasa Y, Yamashita T, Miyamoto Y, Yamamoto A, Tomoike H and Yokoyama S: Impact of statin treatment on the clinical fate of heterozygous familial hypercholesterolemia. J Atheroscler Thromb, 2010; 17:667-674.
  10. Makino H, Harada-Shiba M: Safety aspects of statins: Which factors create the adverse effects of statins. Immun Endoc & Metab in Med Chem 8: 172-176, 2008.
  11. Shimano H, Arai H, Harada-Shiba M, Ueshima H, Ohta T, Yamashita S, Gotoda T, Kiyohara Y, Hayashi T, Kobayashi J, Shimamoto K, Bujo H, Ishibashi S, Shirai K, Oikawa S, Saito Y, Yamada N: Proposed guidelines for hypertriglyceridemia in japan with non-HDL cholesterol as the second target. J Atheroscler Thromb, 2008; 15(3): 116-121.
  12. Yamashita S, Bujo H, Arai H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa Y: Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb 15: 292-303, 2008.
  13. Yamamoto A, Harada-Shiba M, Endo M, Kusakabe N, Tanioka T, Kato H, Shoji T: The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy. Atherosclerosis 186: 126-131, 2006.
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