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Cải thiện chức năng phổi sau khi bổ sung vitamin C cho các bà mẹ mang thai có liên quan đến chuyển methyl hóa DNA miệng ở tuổi 5
Tóm tắt
Chúng tôi đã báo cáo trước đây trong thử nghiệm lâm sàng ngẫu nhiên (RCT) "Vitamin C để giảm tác động của thuốc lá trong thai kỳ đối với chức năng phổi của trẻ sơ sinh" rằng việc bổ sung vitamin C (500 mg/ngày) cho những bà mẹ mang thai hút thuốc có liên quan đến việc cải thiện kết quả hô hấp mà duy trì đến 5 năm tuổi. Mục tiêu của nghiên cứu này là đánh giá xem chuyển methyl hóa DNA tế bào miệng (DNAm), như một dấu ấn cho biểu mô đường dẫn khí, có liên quan đến việc bổ sung vitamin C, cải thiện chức năng phổi và giảm sự xuất hiện của tiếng thở khò khè hay không. Chúng tôi đã thực hiện các nghiên cứu liên kết toàn bộ hệ gen (EWAS) bằng cách sử dụng các mảng Infinium MethylationEPIC và DNAm miệng từ 158 đối tượng (80 nhóm giả dược; 78 nhóm vitamin C) với kiểm tra chức năng phổi (PFT) được thực hiện tại lần thăm khám năm thứ 5. EWAS đã được thực hiện trên (1) điều trị vitamin C, (2) lưu lượng khí thở cưỡng bức giữa 25 và 75% thể tích đã thở ra (FEF25–75), và (3) tiếng thở khò khè ở trẻ. Các mô hình đã được điều chỉnh theo giới tính, chủng tộc, địa điểm nghiên cứu, tuổi thai tại thời điểm ngẫu nhiên hóa (≤ OR > 18 tuần), tỷ lệ tế bào biểu mô, và các biến số tiềm ẩn bên cạnh chiều cao của trẻ tại PFT trong EWAS cho FEF25–75. Chúng tôi coi FDR p < 0.05 là có ý nghĩa đáng kể trên toàn bộ hệ gen và p danh nghĩa < 0.001 là những ứng viên cho các phân tích tiếp theo. DNAm miệng được đo ở một phân nhóm đối tượng tại thời điểm sinh và gần 1 tuổi đã được sử dụng để xác định xem các dấu ấn DNAm xuất phát từ trong tử cung, hay xuất hiện theo tuổi. Việc điều trị vitamin C có liên quan đến 457 DMC (CpGs đã methyl hóa khác biệt có ý nghĩa FDR; 236 hypermethylated; 221 hypomethylated) có ý nghĩa (q < 0.05) và 53 DMR (vùng methyl hóa khác biệt; 26 hyper; 27 hypo) ở tuổi 5. FEF25–75 có liên quan đến một DMC có ý nghĩa FDR (cg05814800), 1,468 DMC ứng viên (p < 0.001), và 44 DMR. Tiếng thở khò khè hiện tại có liên quan đến 0 DMC FDR-DMC, 782 DMC ứng viên, và 19 DMR (p < 0.001). Trong 365/457 DMC quan trọng FDR vitamin C ở tuổi 5, không có tương tác đáng kể giữa thời gian và điều trị. Việc bổ sung vitamin C cho các bà mẹ mang thai hút thuốc có liên quan đến methyl hóa DNA miệng ở trẻ em ở tuổi 5, và hầu hết các dấu ấn methyl hóa dường như kéo dài từ giai đoạn trước khi sinh. Methyl hóa miệng ở tuổi 5 cũng có liên quan đến chức năng phổi hiện tại và sự xuất hiện của tiếng thở khò khè, và những vị trí có liên quan chức năng này dường như tập trung cho các vị trí liên quan đến vitamin C. Đăng ký thử nghiệm lâm sàng trên ClinicalTrials.gov, NCT01723696 và NCT03203603.
Từ khóa
#vitamin C #methyl hóa DNA #chức năng phổi #tiếng thở khò khè #thử nghiệm lâm sàngTài liệu tham khảo
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