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Tương tác đồng sinh của alen HLA-DRB1*07 và đa hình đơn nucleotide TNF-Alpha − 863 C/A trong việc dễ bị mắc bệnh lupus ban đỏ hệ thống
Tóm tắt
Lupus ban đỏ hệ thống (SLE) là một bệnh tự miễn viêm đặc trưng bởi sự mất cân bằng của nhiều cytokine, gây ra các quá trình viêm dẫn đến tổn thương mô. Yếu tố hoại tử khối u alpha (TNF-α) là một trong những cytokine điều hòa miễn dịch quan trọng nhất, đã được liên quan đến các bệnh tự miễn khác nhau, bao gồm SLE. Hai trăm hai bệnh nhân SLE và 318 đối chứng đã được đưa vào nghiên cứu. Vùng promoter gen TNF-α (từ −250 đến −1000 cặp bazơ) đã được phân tích bằng phương pháp giải trình tự DNA trực tiếp Sanger để tìm các biến thể promoter liên quan đến bệnh nhân SLE người Ấn Độ phía Nam. Chúng tôi đã phân tích sáu đa hình di truyền TNF-α, bao gồm −863C/A (rs1800630), −857C/T (rs1799724), −806C/T (rs4248158), −646G/A (rs4248160), −572A/C (rs4248161) và −308G/A (rs1800629) ở cả bệnh nhân SLE và đối chứng. Chúng tôi không tìm thấy mối liên hệ của các SNP promoter gen TNF-α với bệnh nhân SLE. Tuy nhiên, alen −863A (rs1800630) cho thấy mối liên hệ với kiểu hình viêm thận lupus ở bệnh nhân SLE (OR: 1.62, 95%CI 1.04–2.53, P = 0.034). Chúng tôi nhận thấy nồng độ TNF-α huyết thanh tăng đáng kể ở các trường hợp SLE so với đối chứng và không tìm thấy mối liên hệ với bất kỳ đa hình nào. Phân tích haplotype tiết lộ một mối liên hệ bảo vệ đáng kể giữa các alen TNF-α hoang dã ở các vị trí −863C, −857C, −806C, −646G, −572A và −308G (haplotype CCCGAG) với kiểu hình viêm thận lupus (OR 0.53, 95% CI 0.35–0.82, P = 0.004). Thêm vào đó, đa hình TNF-α −863 C/A (rs1800630) và haplotype HLA-DRB1*07 cho thấy sự khác biệt đáng kể giữa bệnh nhân SLE và đối chứng (OR 4.79, 95% CI 1.73–13.29, P = 0.0009). Tóm lại, alen TNF-α −863A (rs1800630) có liên quan đến tăng nguy cơ viêm thận ở bệnh nhân SLE người Ấn Độ phía Nam. Chúng tôi cũng tìm thấy một tương tác giữa alen HLA-DRB1*07 với đa hình promoter TNF-α −863 C/A, cung cấp bằng chứng hỗ trợ cho sự liên kết không đồng đều chặt chẽ giữa các SNP promoter TNF-α và các alen MHC lớp II DRB1.
Từ khóa
#lupus ban đỏ hệ thống #TNF-α #alen HLA-DRB1*07 #viêm thận lupus #đa hình đơn nucleotide #nghiên cứu di truyền họcTài liệu tham khảo
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