Khảo Sát Toàn Bộ Gen Về Các Loci Liên Kết Với Nồng Độ Glucose Và HbA1c Trong Một Mẫu Dân Cư Căn Cứ Người Da Trắng
Tóm tắt
Các mức glucose trong máu cao là dấu hiệu chính của bệnh tiểu đường loại 2 cũng như là một yếu tố nguy cơ mạnh mẽ cho sự phát triển của bệnh này. Chúng tôi đã thực hiện một cuộc tìm kiếm toàn bộ gen cho các gen liên quan đến bệnh tiểu đường, sử dụng các đo lường về glycémie như là các đặc điểm định lượng trong 330 gia đình từ Nghiên Cứu Tim Mạch Framingham. Trong số 3,799 người tham gia tại chu kỳ kiểm tra thứ 5 của Nghiên Cứu Hậu Duệ (1991–1995), 1,461, 1,251 và 771 nam (49%) và nữ đã cung cấp thông tin về mức glucose nhịn ăn trung bình 20 năm, glucose nhịn ăn hiện tại, và HbA1c, tương ứng, và 1,308 người đã đóng góp dữ liệu kiểu gen (sử dụng 401 chỉ thị vi nhân với khoảng cách trung bình 10 cM). Các mức của các đặc điểm glycémique đã được điều chỉnh cho tuổi, việc hút thuốc lá, sử dụng rượu và estrogen, hoạt động thể chất và chỉ số khối cơ thể (BMI). Chúng tôi đã xếp hạng các sai số chuẩn hóa từ các mô hình này, tạo ra các độ lệch chuẩn hóa từ các hạng, và sử dụng mô hình thành phần phương sai được triển khai trong SOLAR (Quy trình Phân tích Liên kết Oligogenic Tuần tự) để đánh giá liên kết với các độ lệch chuẩn hóa như là các đặc điểm định lượng. Chúng tôi tìm thấy bằng chứng đạt đỉnh cho liên kết với các mức glucose nhịn ăn trung bình 20 năm trên nhiễm sắc thể 1 tại khoảng 247 cM từ p-telomere (pter) (logarithm của nguy cơ nhiều điểm [LOD] 2.33) và trên nhiễm sắc thể 10 tại khoảng 86 cM từ pter (LOD nhiều điểm 2.07); với các mức glucose nhịn ăn hiện tại trên nhiễm sắc thể 1 tại khoảng 218 cM từ pter (LOD nhiều điểm 1.80) và trên nhiễm sắc thể 10 tại khoảng 96 cM từ pter (LOD nhiều điểm 2.15); và đối với các mức HbA1c trên nhiễm sắc thể 1 tại khoảng 187 cM (LOD nhiều điểm 2.81). Phân tích này của các gia đình châu Âu không chọn lọc gợi ý việc xác định các loci đặc điểm định lượng ảnh hưởng đến cân bằng glucose trên các nhiễm sắc thể 1q và 10q. Các phát hiện tại khoảng 187–218 cM trên nhiễm sắc thể 1 dường như lặp lại các liên kết đã được báo cáo trong các nghiên cứu trước đây của các quần thể khác, chỉ ra rằng vùng nhiễm sắc thể lớn này cần được xem xét kỹ lưỡng hơn trong việc tìm kiếm các gen nhạy cảm với bệnh tiểu đường loại 2.
Từ khóa
#tiểu đường loại 2 #glucose #HbA1c #gen #nhiễm sắc thể #nghiên cứu di truyềnTài liệu tham khảo
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