Sự biến đổi của metyl hóa DNA PEAR1 ảnh hưởng đến chức năng tiểu cầu và bạch cầu

Springer Science and Business Media LLC - Tập 11 - Trang 1-11 - 2019
Benedetta Izzi1, Francesco Gianfagna2,3, Wen-Yi Yang4, Katrien Cludts5, Amalia De Curtis1, Peter Verhamme5, Augusto Di Castelnuovo2, Chiara Cerletti1, Maria Benedetta Donati1, Giovanni de Gaetano1, Jan A. Staessen4, Marc F. Hoylaerts5, Licia Iacoviello1,3
1Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, Italy
2Mediterranea Cardiocentro, Naples, Italy
3Department of Medicine and Surgery, University of Insubria, Varese, Italy
4Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
5Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

Tóm tắt

Receptor tổng hợp tế bào tiểu cầu - nội mô 1 (PEAR-1) là một thụ thể xuyên màng tham gia vào hoạt hóa tiểu cầu và sinh sản megakaryocyte, có biểu hiện bị ảnh hưởng bởi quá trình metyl hóa DNA. Các biến thể PEAR1 được liên kết với phản ứng tiểu cầu khác nhau đối với sự kích hoạt và các kết cục tim mạch. Mục tiêu của chúng tôi là điều tra mối liên hệ giữa metyl hóa PEAR1 và các chỉ số chức năng tiểu cầu và bạch cầu trong một quần thể gia đình. Chúng tôi đã đo lường metyl hóa PEAR1 ở 605 người tham gia trong gia đình Moli với các số liệu xét nghiệm máu có sẵn, mức độ P-selectin huyết tương và protein C-reactive, cũng như các đo lường P-selectin tiểu cầu trong máu toàn phần và hỗn hợp conjugate tiểu cầu-bạch cầu. Chúng tôi đã thực hiện phân tích thành phần chính (PCA) để xác định các nhóm CpG có tương quan cao. Chúng tôi sử dụng mô hình hồi quy hỗn hợp tuyến tính (với các yếu tố cố định như tuổi, giới tính, BMI, hút thuốc, uống rượu, có vai trò là người được gọi cho tuyển dụng gia đình, là thành viên của gia đình bị nhồi máu cơ tim (MI) và gia đình như một yếu tố ngẫu nhiên) để đánh giá các mối liên hệ giữa metyl hóa PEAR1 và các kiểu hình. Tham số metyl hóa PEAR1 Factor2, được đặc trưng bởi các vị trí CpG đặc hiệu cho megakaryocyte đã được xác định trước, có mối liên hệ ngược với conjugates tiểu cầu-monocyte, P-selectin và tổng số WBC, trong khi có mối liên hệ thuận với độ rộng phân phối tiểu cầu (PDW) và với bạch cầu CD11b và L-selectin. Hơn nữa, metyl hóa PEAR1 Factor2 có liên quan tiêu cực đến INFLAscore, một chỉ số viêm nhẹ. Chỉ số này được trung gian hóa một phần bởi ảnh hưởng metyl hóa PEAR1 lên các biến số tiểu cầu. Mối liên hệ giữa metyl hóa PEAR1 với các số liệu WBC và INFLAscore đã được xác nhận trong nhóm độc lập FLEMENGHO. Chúng tôi báo cáo một liên kết đáng kể giữa các dấu hiệu epigenetic trong gen chức năng tiểu cầu và biến động chức năng tiểu cầu phụ thuộc vào viêm được đo lường trong hai nhóm độc lập.

Từ khóa

#PEAR1 #metyl hóa DNA #chức năng tiểu cầu #chức năng bạch cầu #viêm

Tài liệu tham khảo

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