调脂药物靶点与高血压肾病风险：一项药物靶向孟德尔随机化分析

来源期刊：广州医药 | 881-887 发布时间：2024-09-24 收稿时间：2025/11/17 15:48:22 阅读量：39

作者：: 连兴基,

彭晓辉,

王衍慧,

杨媚,

刘丽兰,

黄玉宇,

关键词：: 调脂药物他汀类药物高血压肾病孟德尔随机化全基因组关联研究; lipid-lowering drugs statins hypertensive nephropathy Mendelian randomization genome-wide association study

DOI：: 10.3969/j.issn.1000-8535.2024.08.009

收稿时间：: 2024-03-06
修订日期：
接收日期：
引用总数：: 0

目的评估调脂药物靶点所介导的脂质表型（HMGCR、PCSK9和NPC1L1）与高血压肾病风险之间潜在的因果相关性。方法使用来自欧洲人群公开可获得的全基因组关联研究（GWAS）汇总数据进行孟德尔随机化（MR）分析。采用与低密度脂蛋白胆固醇（LDL-C）相关的遗传变异,根据选定的调脂药物靶基因筛选工具变量,使用逆方差加权法作为主要MR分析方法,并进行敏感性分析确保结果的稳健性。结果基因预测的LDL-C水平与较高的高血压肾病风险相关（OR=1.19,95% CI：1.03~1.38,P=0.021）。较高的HMGCR介导的LDL-C水平与高血压肾病风险存在正向因果相关性（OR=4.08,95% CI：2.86~5.81;P<0.001）。然而,PCSK9和NPC1L1介导的LDL-C水平与高血压肾病风险无相关性。Cochran Q检验、MR-PRESSO检测和MR-Egger截距测试显示工具变量之间不存在异质性或水平多效性。结论 HMGCR介导的LDL-C与高血压肾病的发病风险存在因果相关性,针对HMGCR基因的他汀类药物在高血压肾病的防治中可能具有潜在益处。

1、 PIRILLO A,CATAPANO A L,NORATA G D.Niemann-pick C1-like 1(NPC1L1)inhibition and cardiovascular diseases[J].Curr Med Chem,2016,23(10):983-999.

2、 VLAD C E,FOIA L,POPESCU R,et al.Apolipoproteins A and B and PCSK9:Nontraditional cardiovascular risk factors in chronic kidney disease and in end-stage renal disease[J].J Diabetes Res,2019(2019):6906278.

3、 LIU C,CHEN J,CHEN H,et al.PCSK9 inhibition:From current advances to evolving future[J].Cells,2022,11(19):2972.

4、 KHAN Z,GUL A,MLAWA G,et al.Statins As anti-hypertensive therapy:A systematic review and meta-analysis[J].Cureus,2024,16(4):e57825.

5、 LIU C,SHEN M,TAN W L W,et al.Statins improve endothelial function via suppression of epigenetic-driven EndMT[J].Nat Cardiovasc Res,2023,2(5):467-485.

6、 OESTERLE A,LAUFS U,LIAO J K.Pleiotropic effects of statins on the cardiovascular system[J].Circ Res,2017,120(1):229-243.

7、 THEOFILIS P,VORDONI A,KOUKOULAKI M,et al.Dyslipidemia in chronic kidney disease:Contemporary concepts and future therapeutic perspectives[J].Am J Nephrol,2021,52(9):693-701.

8、 FULARSKI P,KRZEMI?SKA J,LEWANDOWSKA N,et al.Statins in chronic kidney disease-effects on atherosclerosis and cellular senescence[J].Cells,2023,12(13):1679.

9、 ORTIZ A,WANNER C,GANSEVOORT R,et al.Chronic kidney disease as cardiovascular risk factor in routine clinical practice:A position statement by the Council of the European Renal Association[J].Nephrol Dial Transplant,2023,38(3):527-531.

10、 LIAO G,WANG X,LI Y,et al.Antidyslipidemia pharmacotherapy in chronic kidney disease:A systematic review and Bayesian network meta-Analysis[J].Pharmaceutics,2022,15(1):6.

11、 HWANG S D,KIM K,KIM Y J,et al.Effect of statins on cardiovascular complications in chronic kidney disease patients:A network meta-analysis[J].Medicine(Baltimore),2020,99(22):e20061.

12、邱秀君,陈越,冯文才.药物服务干预对老年高血压患者的治疗及用药安全性的影响[J].广州医药,2023,54(12):49-54.

13、中华医学会心血管病学分会高血压学组,中华心血管病杂志编辑委员会.中国高血压患者血压血脂综合管理的专家共识.中华心血管病杂志,2021,49(6):10:54-563.

14、 VERBANCK M,CHEN C Y,NEALE B,et al.Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J].Nat Genet,2018,50(5):693-698.

15、 BURGESS S,DUDBRIDGE F,THOMPSON S G.Combining information on multiple instrumental variables in Mendelian randomization:Comparison of allele score and summarized data methods[J].Stat Med,2016,35(11):1880-1906.

16、 GRAHAM S E,CLARKE S L,WU K H,et al.The power of genetic diversity in genome-wide association studies of lipids[J].Nature,2021(600):675-679.

17、 GALLEGO-COLON E,DAUM A,YOSEFY C.Statins and PCSK9 inhibitors:A new lipid-lowering therapy[J].Eur J Pharmacol,2020(878):173114.

18、 SKRIVANKOVA V W,RICHMOND R C,WOOLF B A R,et al.Strengthening the reporting of observational studies in epidemiology using Mendelian randomization:The STROBE-MR statement[J].JAMA,2021,326(16):1614-1621.

19、 FERENCE B A.Interpreting the clinical implications of drug-target Mendelian randomization studies[J].J Am Coll Cardiol,2022,80(7):663-665.

20、 DAVEY SMITH G,HEMANI G.Mendelian randomization:Genetic anchors for causal inference in epidemiological studies[J].Hum Mol Genet,2014,23(R1):R89-R98.

21、 GHAYDA R A,LEE J Y,YANG J W,et al.The effect of statins on all-cause and cardiovascular mortality in patients with non-dialysis chronic kidney disease,patients on dialysis,and kidney transplanted recipients:An umbrella review of meta-analyses[J].Eur Rev Med Pharmacol Sci,2021(25):2696-2710.

22、 SU X,ZHANG L,LV J,et al.Effect of statins on kidney disease outcomes:A systematic review and meta-analysis[J].Am J Kidney Dis,2016(67):881-892.

23、 ZHOU S,SU L,XU R,et al.Statin initiation and risk of incident kidney disease in patients with diabetes[J].CMAJ,2023,195(21):E729-E738.

24、李晓鹏,张修齐,张敏华,等.老年高血压患者社区健康管理模式研究进展[J].现代医院,2024,24(3):452-456.

25、 BU Y,LIU Y,ZHOU M,et al.The burden of hypertension-related chronic kidney disease - China,2010-2019[J].China CDC Wkly,2024,6(14):282-288.

26、高血压肾病诊治中国专家共识组成员.高血压肾病诊断和治疗中国专家共识(2022).中华高血压杂志,2022,30(4):307-317.