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A novel method for determining functional LDL receptor activity in familial hypercholesterolemia: Application of the CD3/CD28 assay in lymphocytes
- フォーマット:
- 論文
- 責任表示:
- Tada, Hayato ; Kawashiri, Masaaki ; Noguchi, Tohru ; Mori, Mika ; Tsuchida, Masayuki ; Takata, Mutsuko ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yachie, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
- 言語:
- 英語
- 出版情報:
- Elsevier, 2009-02-01
- 著者名:
Tada, Hayato Kawashiri, Masaaki Noguchi, Tohru Mori, Mika Tsuchida, Masayuki Takata, Mutsuko Nohara, Atsushi Inazu, Akihiro Kobayashi, Junji Yachie, Akihiro Mabuchi, Hiroshi Yamagishi, Masakazu - 掲載情報:
- Clinica Chimica Acta
- ISSN:
- 0009-8981
- 巻:
- 400
- 通号:
- 1-2
- 開始ページ:
- 42
- 終了ページ:
- 47
- バージョン:
- author
- 概要:
- 金沢大学附属病院循環器内科<br />Background: The objective of this study was to develop a new and simple method for measuring low-density lipoprotein receptor (LDLR) activity using peripheral lymphocytes enabling us to clinically diagnose familial … hypercholesterolemia (FH) and ascertain the involved mutations (such as K790X mutation), that might not be clearly detected in the conventional method. Methods: Our method comprised the following 2 features: first, we used anti-CD3/CD28 beads to stimulate T-lymphocytes to obtain a uniform fraction of lymphocytes and maximum up-regulation of LDLR. Second, we excluded the possibility of overestimation of lymphocyte signals bound only to its surface, by adding heparin to the cultured lymphocytes used for the LDLR assay. Results: Based on the genetic mutation, the FH subjects were divided into 2 groups, K790X, (n = 20) and P664L, (n = 5), and their LDLR activities was measured by this method, which was found to be 55.3 ± 8.9% and 63.9 ± 13.8%, respectively, of that of the control group (n = 15). In comparison, the LDLR activity was 86.1 ± 11.6% (K790X) and 73.3 ± 6.3% (P664L) of that of the control group when measured by the conventional method, indicating that impairment of LDLR function in FH K790X subjects was much more clearly differentiated with our method than with the conventional method (paired t-test, p < 0.0001). The levels of LDLR expression also showed similar tendencies, that is, 89.4 ± 13.2% (K790X) and 76.9 ± 17.4% (P664L) of that of the control group when measured by the conventional method, and 78.1 ± 9.7% (K790X) and 70.3 ± 26.5% (P664L) when measured by our new method. In addition, we confirmed that there was little influence of statin treatment on LDLR activity among the study subjects when our method was used. Conclusion: These results demonstrate that our new method is applicable for measuring LDLR activity, even in subjects with an internally defective allele, and that T-lymphocytes of the FH K790X mutation possess characteristics of that allele. © 2008 Elsevier B.V. All rights reserved. 続きを見る
- URL:
- http://hdl.handle.net/2297/14392
類似資料:
Japan Atherosclerosis Society = 日本動脈硬化学会 | |
Japanese Circulation Society = 日本循環器学会 | |
Japanese Circulation Society = 日本循環器学会 |
Japan Atherosclerosis Society = 日本動脈硬化学会 |