Tương tác gen-môi trường giữa ERCC2, ERCC3, XRCC1 và sự tiếp xúc với cadmium trong bệnh polyp mũi

Journal of Applied Genetics - Tập 58 - Trang 221-229 - 2016
Rim Khlifi1,2, Pablo Olmedo3, Fernando Gil3, Boutheina Hammami4, Amel Hamza-Chaffai1, Ahmed Rebai2
1Unit of Marine and Environmental Toxicology, UR 09-03, Institut Préparatoire aux Etudes d’Ingénieur de Sfax (IPEIS), Sfax, Tunisia
2Laboratory of Molecular and Cellular screening Processes, Centre of Biotechnology of Sfax, Sfax, Tunisia
3Department of Legal Medicine and Toxicology, University of Granada, Granada, Spain
4Department of Otorhinolaryngology, Habib Bourguiba Hospital, Sfax, Tunisia

Tóm tắt

Tương tác giữa gen và môi trường từ lâu đã được biết đến là có vai trò quan trọng trong nguyên nhân sinh bệnh của các bệnh phức tạp, chẳng hạn như polyp mũi (NP). Nghiên cứu hiện tại ủng hộ khái niệm rằng các biến thể di truyền của gen sửa chữa ADN có vai trò quan trọng trong việc điều chỉnh độ nhạy cảm của từng cá nhân với các bệnh do môi trường gây ra. Thực tế, chúng tôi đã điều tra vai trò của các biến thể di truyền trong gen sửa chữa ADN và cadmium như các yếu tố nguy cơ đối với bệnh nhân Tunisia bị NP. Theo những gì chúng tôi biết, đây là báo cáo đầu tiên về tác động của các hiệu ứng kết hợp giữa cadmium và các biến thể gen ERCC3 7122 A>G (rs4150407), ERCC2 Lys751Gln (rs13181) và XRCC1 Arg399Gln (rs25487) đối với độ nhạy cảm với bệnh NP. Những liên kết có ý nghĩa giữa nguy cơ phát triển bệnh NP và các kiểu gen ERCC2 [tỷ lệ chênh lệch (OR)= 2.0, khoảng tin cậy (CI) 95% = 1.1–3.7, p = 0.023] và ERCC3 (OR = 2.2, 95% CI = 1.2–4.1, p = 0.013) đã được quan sát thấy. Nồng độ cadmium trong máu của bệnh nhân NP (2.2 μg/L) cao hơn đáng kể so với nhóm đối chứng (0.5 μg/L). Một tương tác có ý nghĩa giữa biến thể di truyền ERCC3 (7122 A>G) và nồng độ cadmium trong máu (đối với lượng trung bình của nồng độ cadmium trong máu: OR = 3.8, 95% CI = 1.3–10.8, p = 0.014 và cho các phần trăm 75 của nồng độ cadmium trong máu: OR = 2.7, 95% CI = 1.1–7.2, p = 0.041) đã được phát hiện liên quan đến nguy cơ bệnh NP. Thêm vào đó, khi chúng tôi phân tầng các kiểu gen biến thể di truyền của ERCC2, ERCC3 và XRCC1 theo lượng trung bình và phần trăm 75 của nồng độ cadmium trong máu, chúng tôi cũng tìm thấy những tương tác có ý nghĩa giữa các kiểu gen biến thể di truyền ERCC2 (Lys751Gln) và ERCC3 (7122 A>G) với kim loại này liên quan đến bệnh NP. Tuy nhiên, không có tương tác nào được tìm thấy giữa các kiểu gen biến thể di truyền XRCC1 (Arg399Gln) và cadmium liên quan đến bệnh NP.

Từ khóa

#gene environment interactions #nasal polyposis #ERCC2 #ERCC3 #XRCC1 #cadmium #genetic polymorphisms #risk factors

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