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匡昱林, 王宇凰, 欧梁, 李洪芳, 熊罗节, 龚智超, 孙绍裘.基于肾主骨理论探讨肾病与骨质疏松症因果关系的孟德尔随机化分析[J].湖南中医药大学学报,2024,44(7):1247-1253[点击复制] |
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| 基于肾主骨理论探讨肾病与骨质疏松症因果关系的孟德尔随机化分析 |
| 匡昱林,王宇凰,欧梁,李洪芳,熊罗节,龚智超,孙绍裘 |
| (湖南中医药大学第二附属医院, 湖南 长沙 410005;湖南中医药大学, 湖南 长沙 410208;湖南省中医药研究院, 湖南 长沙 410013;北京中医药大学, 北京 100029;遵义医科大学, 贵州 遵义 563006) |
| 摘要: |
| 目的 探索中医肾主骨理论下，肾病与骨质疏松症（osteoporosis, OP）的因果关系。方法 使用孟德尔随机化方法，从全基因组关联研究（genome-wide association study, GWAS）数据库筛选肾病相关单核苷酸多态性（single nucleotide polymorphisms, SNPs）作为工具变量，应用固定效应逆方差加权及多种敏感性分析以评估肾病与OP之间的因果关系。结果 5种孟德尔随机化分析结果显示，膜性肾病（OR=1.000 6，95%CI：1.000 2~1.000 9，P=0.001 0）、慢性肾小球肾炎（OR=1.000 8，95%CI：1.000 1~1.001 5，P=0.038 0）、糖尿病肾病（OR=1.001 0，95%CI：1.000 1~1.002 0，P=0.031 6）、血清肌酐升高（OR=1.013 0，95%CI：1.000 0~1.026 0，P=0.050 8）可显著增加OP风险，估计的肾小球滤过率升高则与OP风险降低相关（OR=0.997 0，95%CI：0.995 3~0.998 6，P=0.000 3）。多重敏感性分析证实了结果的稳健性，未发现明显的多效性（MR-Egger截距P>0.05）和异质性（Cohran's Q检验P>0.05）。结论 肾病与OP间存在正向因果关系，佐证肾主骨理论，为肾病相关OP预防和治疗提供新证据。 |
| 关键词: 骨质疏松症 慢性肾病 肾功能 孟德尔随机化 中医理论 |
| DOI：10.3969/j.issn.1674-070X.2024.07.015 |
| 投稿时间：2024-03-05 |
| 基金项目:中国博士后科学基金面上项目（2023M731070）；湖南省临床医疗技术创新引导项目（2021SK51301）；湖南中医药大学研究生创新课题立项项目（2022CX41）。 |
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| Mendelian randomization analysis of the causal relationship between kidney disease and osteoporosis based on the theory of kidney governing bones |
| KUANG Yulin, WANG Yuhuang, OU Liang, LI Hongfang, XIONG Luojie, GONG Zhichao, SUN Shaoqiu |
| (The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Academy of Chinese Medicine, Changsha, Hunan 410013, China;Beijing University of Chinese Medicine, Beijing 100029, China;Zunyi Medical University, Zunyi, Guizhou 563006, China) |
| Abstract: |
| Objective To explore the causal relationship between kidney disease and osteoporosis (OP) under the Chinese medicine theory of kidney governing bones. Methods Using the Mendelian randomization approach, single nucleotide polymorphisms (SNPs) related to kidney disease were screened as instrumental variables from the genome-wide association study (GWAS) database. Additionally, the fixed-effect inverse variance weighted method and multiple sensitivity analyses were employed to assess the causal relationship between kidney disease and osteoporosis (OP). Results Five kinds of Mendelian randomization analyses revealed that membranous nephropathy (OR=1.000 6, 95% CI: 1.000 2~1.000 9, P=0.001 0), chronic glomerulonephritis (OR=1.000 8, 95% CI: 1.000 1~1.001 5, P=0.038 0), diabetic nephropathy (OR=1.001 0, 95% CI: 1.000 1~1.002 0, P=0.031 6), and elevated serum creatinine (OR=1.0130, 95% CI: 1.000 0~1.026 0, P=0.050 8) can significantly increase the risk of OP, while an estimated increase in glomerular filtration rate was associated with a lower risk of OP (OR=0.997 0, 95% CI: 0.995 3~0.998 6, P=0.000 3). Multiple sensitivity analyses confirmed the robustness of the results, with no notable pleiotropy (MR-Egger intercept P>0.05) or heterogeneity (Cohran's Q test P>0.05) identified. Conclusion This study confirms a positive causal relationship between kidney disease and OP, supporting the theory of kidney governing bones. Thus, it provides new evidence for the prevention and treatment of kidney disease-related OP. |
| Key words: osteoporosis chronic kidney disease kidney function Mendelian randomization Chinese medicine theory |
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