Khảo sát tài liệu để phân tích con đường tổng quát: Nghiên cứu trường hợp thu thập các gen liên quan đến homocysteine cho các nghiên cứu di truyền và epigenetic

Priyanka Sharma1, RD Senthilkumar1, Vani Brahmachari2, Elayanambi Sundaramoorthy1, Anubha Mahajan1, Amitabh Sharma1, Shantanu Sengupta1
1Department of Proteomics and Structural Biology, Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
2Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India

Tóm tắt

Homocysteine là một yếu tố nguy cơ độc lập đối với các bệnh tim mạch. Nó cũng được biết đến là liên quan đến nhiều rối loạn phức tạp khác nhau. Mặc dù có rất nhiều nghiên cứu độc lập chỉ ra vai trò của homocysteine trong các con đường riêng lẻ, cơ chế gây hại do homocysteine vẫn chưa được làm rõ. Việc điều chỉnh biểu hiện gen do homocysteine thông qua việc thay đổi trạng thái methylation hoặc bằng các cơ chế chưa được biết đến dự đoán sẽ dẫn đến nhiều tình trạng bệnh lý, trực tiếp hoặc gián tiếp. Trong bản thảo hiện tại, bằng cách sử dụng phương pháp khai thác tài liệu, chúng tôi đã xác định các gen bị điều chỉnh trực tiếp hoặc gián tiếp bởi mức homocysteine cao. Các gen này sau đó được đặt vào các con đường phù hợp nhằm hiểu cơ sở phân tử của các rối loạn phức tạp do homocysteine gây ra và cung cấp tài nguyên cho việc chọn lọc các gen để kiểm tra đa hình cũng như phân tích đột biến cũng như các sửa đổi epigenetic liên quan đến hyperhomocysteinemia. Chúng tôi đã xác định được 135 gen trong 1137 bản tóm tắt có thể điều chỉnh mức homocysteine hoặc bị tác động bởi mức homocysteine cao. Việc lập bản đồ các gen đến các con đường tương ứng cho thấy mức homocysteine cao dẫn đến xơ vữa động mạch, có thể là do ảnh hưởng trực tiếp đến chuyển hóa và vận chuyển lipid hoặc thông qua stress oxy hóa và/hoặc stress Lưới nội đồng (ER). Mức homocysteine cao cũng làm giảm khả năng sinh học của nitric oxide và điều chỉnh mức của các chất chuyển hóa khác bao gồm S-adenosyl methionine và S-adenosyl homocysteine, điều này có thể dẫn đến các rối loạn tim mạch hoặc thần kinh. Stress ER nổi lên như một con đường chung liên quan đến apoptosis, xơ vữa động mạch và các rối loạn thần kinh và bị điều chỉnh bởi mức homocysteine. Mạng lưới tổng hợp đã thu thập cho thấy các gen bị điều chỉnh bởi homocysteine, cho thấy rằng homocysteine tác động không chỉ bằng cách điều chỉnh mức nền tảng cho các quá trình xúc tác khác nhau mà còn thông qua việc điều chỉnh biểu hiện của các gen liên quan đến các bệnh phức tạp.

Từ khóa


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