Đa hình gen CYP3A5 và nồng độ tacrolimus ở bệnh nhân ghép thận

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Tác giả: Thị Thu Hán, Đình Hiếu Lê, Thị Thanh Thùy Nguyễn

Ngôn ngữ: vie

Ký hiệu phân loại:

Thông tin xuất bản: Tạp chí Y học lâm sàng Bệnh viện Trung ương Huế, 2024

Mô tả vật lý: tr.51-55

Bộ sưu tập: Metadata

ID: 372029

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Background: Tarolimus (Tac), a calcineurin inhibitor, is the cornerstone of most immunosuppressive regimens following renal transplantation. Tac metabolism is closely related to the presence of the enzyme CYP3A5 in the liver and intestines. The study aimed to determine the CYP3A5 genetic polymorphism and the relationship between dose and trough concentration (C0) Tac as well as intrapatient variability of tacrolimus (IPV Tac) with CYP3A5 polymorphism. Methods: 76 kidney transplant patients from living donors at the Department of Nephrology and Transplant Immunology, People’s Hospital 115, from December 2018 to May 2021, were sequenced for the CYP3A5 gene and had at least 3 C0 Tac from 7th to 12th month post-transplant were included in the study. Simultaneously we recorded the Tac dose and IPV Tac from the 7th to the 12th month post - transplant. Results: The proportions of genotypes CYP3A5/1*1, /1*3 (expresser group) and /3*3 (non - expresser group) were 11.8%, 32.9% and 55.3%, respectively. There were no differences in CYP3A5 genotypes between males and females. The mean Tac dose was higher significant in the expresser group (6,36 ± 0,4mg) compared with the non - expresser group (3,94 ± 0,27mg) (p = 0.001), while the mean C0 Tac was lower in the expresser group (8,08 ± 0,29 ng/mL) compared with the non - expresser group (99,34 ± 0,31 ng/mL) (p = 0.008). The mean IPV Tac was 17.9 ± 9.7% (range 3.4% - 55.8%). IPV Tac was not statistically significant between groups with and without CYP3A5 expression due to the small sample size and most patients with low IPV Tac (<
20%). Conclusion: Expression of CYP3A5 enzyme (in genotypes CYP3A5/1*1 and /1*3) is very common (1 in 2 kidney transplant patients) and affects dose and Tac concentration in kidney transplant patients.Đặt vấn đề: Tarolimus (Tac), thuộc nhóm ức chế calcineurin, là thuốc ức chế miễn dịch nền tảng trong hầu hết các phác đồ ức chế miễn dịch sau ghép thận. Chuyển hóa Tac liên quan chặt chẽ với sự hiện diện của men CYP3A5 ở gan và ruột. Nghiên cứu nhằm xác định tính đa hình gen CYP3A5 và liên quan giữa liều và nồng độ đáy (C0) Tac với tính đa hình gen CYP3A5. Đối tượng, phương pháp: 76 BN ghép thận từ người hiến thận sống tại Khoa Thận - Miễn dịch ghép BV Nhân Dân 115 từ 12/2018 đến 05/2021, được giải trình tự gen CYP3A5 và có ít nhất 3 C0 Tac từ tháng 7 đến tháng 12 sau ghép được đưa vào nghiên cứu. Ghi nhận đồng thời liều dùng Tac và độ biến thiên nội tại (IPV: intrapatient variability) nồng độ đáy Tac từ tháng 7 đến tháng 12 sau ghép. Kết quả: Tỷ lệ các kiểu gen CYP3A5/1*1, /1*3 và /3*3 lần lượt là 11,8%, 32,9% và 55,3%. Không có khác biệt về kiểu gen CYP3A5 giữa nam và nữ. Liều dùng Tac trung bình cao hơn ở nhóm biểu hiện (6,36 ± 0,4mg) so với nhóm không biểu hiện men CYP3A5 (3,94 ± 0,27mg) (p = 0,001), trong khi C0 Tac trung bình thấp hơn ở nhóm biểu hiện (8,08 ± 0,29 ng/mL) so với nhóm không biểu hiện men CYP3A5 (9,34 ± 0,31 ng/mL) (p = 0,008). IPV trung bình là 17,9 ± 9,7% (biên độ 3,4% - 55,8%). IPV không khác biệt có ý nghĩa thống kê giữa nhóm có và không biểu hiện men CYP3A5 do cỡ mẫu từng nhóm nhỏ và hầu hết BN có IPV thấp (<
20%). Kết luận: Biểu hiện men CYP3A5 rất thường gặp (1 trên 2 BN ghép thận) và có ảnh hưởng đến liều dùng và nồng độ Tac ở BN ghép thận

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