Phân tích di truyền các gen ứng cử viên làm biến đổi tuổi khởi phát bệnh Huntington

Springer Science and Business Media LLC - Tập 120 - Trang 285-292 - 2006
Silke Metzger1, Peter Bauer1, Jürgen Tomiuk1, Franco Laccone2, Stefano DiDonato3, Cinzia Gellera3, Caterina Mariotti3, Herwig W. Lange4, Helga Weirich-Schwaiger5, Gregor K. Wenning6, Klaus Seppi6, Bela Melegh7, Viktoria Havasi7, Laszlo Balikó7,8, Stefan Wieczorek9, Jacek Zaremba10, Dorota Hoffman-Zacharska10, Anna Sulek10, A. Nazli Basak11, Esra Soydan11, Jana Zidovska12, Vera Kebrdlova12, Massimo Pandolfo13, Pascale Ribaï13, Ludovit Kadasi14, Marta Kvasnicova15, Bernhard H. F. Weber16,17, Friedmar Kreuz18, Matthias Dose19, Manfred Stuhrmann20, Olaf Riess1
1Department of Medical Genetics, University of Tübingen, Tübingen, Germany
2Institute of Human Genetics, University of Göttingen, Göttingen, Germany;
3National Institute of Neurology Carlo Besta, Milano, Italy
4air-Rehazentrum, Düsseldorf, Germany
5Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
6Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
7Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary
8Department of Neurology, Csolnoky Ferenc County Hospital, Veszprem, Hungary
9Department of Human Genetics, University of Bochum, Bochum, Germany
10Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland
11Department of Molecular Biology and Genetics, Bogazici University Bebek Istanbul, Istanbul, Turkey
12Institute of Biology and Medical Genetics, 1st Medical Faculty of Charles University and Teaching Hospital, Prague, Czech Rebublic
13Department of Neurology, Erasme Hospital, Brussels, Belgium
14Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia
15Department of Clinical Genetics, Banska Bystrica, Slovakia
16Institute of Human Genetics, University of Würzburg, Würzburg, Germany
17Institute of Human Genetics, University of Regensburg, Regensburg, Germany
18Klinikum für Psychiatrie, Klinikum Chemnitz, Chemnitz, Germany
19BKH-Taufkirchen, Taufkirchen, Germany
20Institute of Human Genetics, University of Hannover, Hannover, Germany

Tóm tắt

Sự mở rộng của sự lặp lại CAG đa hình trong gen HD mã hóa protein huntingtin đã được xác định là nguyên nhân chính gây ra bệnh Huntington (HD) và quyết định 42–73% sự khác biệt về độ tuổi khởi phát bệnh. Các đột biến đa hình ở huntingtin và các gen liên quan được cho là có khả năng làm biến đổi diễn biến của bệnh. Để xác định các yếu tố di truyền làm ảnh hưởng đến tuổi khởi phát bệnh, chúng tôi đã tìm kiếm các dấu hiệu đa hình trong các gen GRIK2, TBP, BDNF, HIP1 và ZDHHC17 và phân tích bảy gen trong số này thông qua các nghiên cứu liên kết trên 980 bệnh nhân HD Châu Âu độc lập. Trong quá trình sàng lọc các biến thể trình tự chưa biết, bên cạnh một số biến thể im lặng, chúng tôi đã phát hiện ba đột biến đa hình trong gen ZDHHC17. Các đột biến này cùng với các đa hình trong gen GRIK2, TBP và BDNF đã được phân tích liên quan đến tuổi khởi phát bệnh HD. Mặc dù một số yếu tố đã được xác định là các yếu tố di truyền điều chỉnh trong các nghiên cứu trước đây, không có gen mã hóa GRIK2, TBP, BDNF và ZDHHC17 nào được xác định là yếu tố điều chỉnh di truyền cho bệnh HD.

Từ khóa

#bệnh Huntington #gen HD #đa hình #tuổi khởi phát #nghiên cứu di truyền

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