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脂代谢与肝生长因子：孟德尔随机化研究
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Abstract:
背景：脂代谢异常与多种肝脏疾病的关系备受关注。研究表明，脂质代谢异常通常与肝脏的储备功能降低有关。肝生长因子对于肝脏的生长和修复至关重要，然而，当前的研究尚未明确证实脂代谢水平异常与肝生长因子功能衰退之间的直接因果联系。在肝脏疾病的研究中，总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和甘油三酯(TG)等脂质代谢指标扮演着关键角色。方法：本研究利用全基因组关联研究(GWAS)数据，旨在深入探讨甘油三酯、总胆固醇、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)与肝生长因子(HGF)之间的关系。我们将遗传变异作为工具变量，通过孟德尔随机化(MR)方法评估胆固醇水平与肝生长因子之间的因果关系。本研究选择逆方差加权(IVW)方法作为主要的分析工具。我们采用了MR-Egger回归、关联性分析和连锁不平衡检测等方法。还进行了F检验，水平多效性和异质性等检测。结果：随机效应IVW结果为TC-HGF：比值比(OR) = 0.887，95%置信区间(CI) = [0.795, 0.991]，P = 0.034，LDL-C-HGF：比值比(OR) = 0.862，95%置信区间(CI) = [0.771, 0.964]，P = 0.009，证明TC和HGF之间存在负相关，且我们发现是LDL-C和HGF存在负相关。结论：本研究结果显示，基因预测的较高胆固醇水平，特别是低密度脂蛋白胆固醇(LDL-C)，与肝生长因子(HGF)风险间存在负向关系。
Background: The relationship between abnormal lipid metabolism and various liver diseases has attracted much attention. Studies have shown that abnormal lipid metabolism is usually related to the decrease of liver reserve function. Liver growth factor is very important for the growth and repair of liver, 4, 5. However, the current research has not clearly confirmed the direct causal relationship between abnormal lipid metabolism level and the decline of liver growth factor function. In the study of liver diseases, lipid metabolism indexes such as total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) play a key role. Method: In this study, genome-wide association studies (GWAS) data 7 was used to explore the relationship between triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) and liver growth factor (HGF). We used genetic variation as a tool variable to evaluate the causal relationship between cholesterol level and liver growth factor by Mendelian randomization (MR). In this study, the inverse variance weighted (IVW) method is selected as the main analysis tool. We used MR-Egger regression, correlation analysis and linkage disequilibrium detection. F test, horizontal pleiotropy and heterogeneity were also carried out. Result: The result of random effect IVW is TC-HGF: odds ratio (OR) = 0.887, 95% confidence interval (CI) = [0.795, 0.991], P = 0.034, LDL-C-HGF: odds ratio (OR) = 0.862, 95% confidence interval (CI) = [0.771, 0.964], P = 0.009, which proves that there is a negative correlation between TC and HGF, and we find that LDL-C and HGF have a negative correlation. Conclusion: The results of
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