Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Phân tích biểu genome của các loại tế bào máu riêng lẻ tiết lộ dấu hiệu hút thuốc B cell cực kỳ cụ thể và liên kết với nguy cơ bệnh tật
Tóm tắt
Hút thuốc lá làm thay đổi hồ sơ methyl hóa DNA của các tế bào miễn dịch, điều này có thể góp phần vào một số cơ chế bệnh sinh của các bệnh liên quan đến smoking. Để liên kết các hiệu ứng di truyền điều chỉnh bởi hút thuốc trong các loại tế bào miễn dịch cụ thể với nguy cơ bệnh tật, chúng tôi đã tách rời sáu kiểu phụ bạch cầu, bao gồm CD14+ tế bào đơn nhân, CD15+ bạch cầu hạt, CD19+ tế bào B, CD4+ tế bào T, CD8+ tế bào T, và CD56+ tế bào giết tự nhiên, từ máu toàn phần của 67 người trưởng thành khỏe mạnh hút thuốc và 74 người không hút thuốc để tiến hành nghiên cứu liên kết toàn bộ genome (EWAS) sử dụng các mảng methyl hóa Illumina 450k và EPIC. Số lượng các vị trí methyl hóa khác biệt liên quan đến hút thuốc (smCpGs) với độ ý nghĩa toàn genome (p < 1.2 × 10−7) thay đổi rộng rãi giữa các loại tế bào, từ 5 smCpGs trong tế bào T CD8+ đến 111 smCpGs trong tế bào B CD19+. Chúng tôi phát hiện các hiệu ứng hút thuốc độc nhất ở mỗi loại tế bào, một số trong đó không rõ ràng trong máu toàn phần. Việc phân tích đặt cược dựa trên methyl hóa để ước tính các kiểu phụ tế bào B cho thấy rằng những người hút thuốc có 7.2% (p = 0.033) ít tế bào B non naïve hơn. Việc điều chỉnh tỷ lệ tế bào B naïve và tế bào B ghi nhớ trong EWAS và RNA-seq cho phép xác định các gen giàu có cho các con đường tín hiệu cytokine liên quan đến kích hoạt tế bào B, phản ứng Th1/Th2, và các bệnh ung thư huyết học. Tích hợp với các bộ dữ liệu công cộng quy mô lớn, 62 smCpGs nằm trong số các CpGs liên quan đến các EWAS có liên quan đến sức khỏe. Hơn nữa, 74 smCpGs có những biến thể dị hợp tử gen số lượng chính xác (SNPs) có thể tái tạo được, mà hoàn toàn ràng buộc với các SNP trong nghiên cứu liên kết toàn bộ genome, gắn liền với chức năng phổi, nguy cơ bệnh tật, và các đặc điểm khác. Chúng tôi quan sát các smCpGs riêng biệt theo chủng loại tế bào máu, sự chuyển đổi từ tế bào B non naïve sang ghi nhớ, và qua việc tích hợp các bộ dữ liệu toàn bộ genome, chúng tôi đã xác định các liên kết tiềm năng của chúng với nguy cơ bệnh tật và các đặc điểm sức khỏe.
Từ khóa
#hút thuốc #methyl hóa DNA #tế bào miễn dịch #nguy cơ bệnh tật #nghiên cứu liên kết toàn bộ genomeTài liệu tham khảo
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