河南省胸科医院,河南省郑州市,450003;
摘要:心血管疾病是全球人类健康的重大威胁,研发新型有效药物对于改善患者预后至关重要。孟德尔随机化作为一种新兴的分析方法,在心血管疾病药物靶点筛选中具有独特优势。本文从孟德尔随机化基础、其在心血管疾病药物靶点筛选中的应用优势、具体研究进展以及局限性等方面进行综述,旨在为心血管疾病药物研发提供新思路和方向。
关键词:孟德尔随机化;心血管疾病;药物靶点筛选
参考文献
[1]GOLDSBOROUGH E,3RD,OSUJI N,BLAHA M J.Assessment of Cardiovascular Disease Risk:A 2022 Update[J].Endocrinol Metab Clin North Am,2022,51(3):483-509.
[2]SIASOS G,BLETSA E,STAMPOULOGLOU P K,et al.MicroRNAs in cardiovascular disease[J].Hellenic J Cardiol,2020,61(3):165-73.
[3]RESTREPO TIQUE M,ARAQUE O,SANCHEZ-ECHEVERRI L A.Technological Advances in the Diagnosis of Cardiovascular Disease:A Public Health Strategy [J].Int J Environ Res Public Health,2024,21(8).
[4]SCHENONE M,DANČíK V,WAGNER B K,CLEMONS P A.Target identification and mechanism of action in chemical biology and drug discovery[J].Nat Chem Biol,2013,9(4):232-40.
[5]LARSSON S C,BUTTERWORTH A S, BURGESS S. Mendelian randomization for cardiovascular diseases: principles and applications [J].Eur Heart J,2023,44(47):4913-24.
[6]杜凯豪-,侯立朝-,罗兰明慧-,et al.-孟德尔随机化在胰腺癌研究中的应用现状与展望[J].-临床肝胆病杂志,2024,-40(-10):-2127.
[7]NAVARESE E P, VINE D, PROCTOR S, et al. Independent Causal Effect of Remnant Cholesterol on Atherosclerotic Cardiovascular Outcomes:A Mendelian Randomization Study [J].Arterioscler Thromb Vasc Biol,2023,43(9):e373-e80.
[8]LEE P C,JUNG I H,THUSSU S,et al.Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease [J]. iScience,2024,27(7):110104.
[9]LI J,ZENG Y,ZHANG D.Association between gynecological cancers and female infertility: insights from bidirectional Mendelian randomization analysis [J].BMC Womens Health,2025,25(1):191.
[10]段圆圆,饶泽辉,邹志明.骨关节炎和阿尔茨海默病关系的双向孟德尔随机化研究[J].老年医学研究,2024,5(05):28-32.
[11]BOEHM F J,ZHOU X.Statistical methods for Mendelian randomization in genome-wide association studies:A review [J].Comput Struct Biotechnol J,2022,20:2338-51.
[12]南霜,郑王.宫颈癌与免疫细胞表型的孟德尔随机化研究[J].2025.
[13]徐艺耘,刘振球, 樊虹,et al.MR-Egger回归在孟德尔随机化分析中的应用[J].复旦学报(医学版), 2021,48(6): 804-9.
[14]WILLIS S C, HORN R L, HESS J E, et al. Heritability and genomic basis of age-at-maturity in Chinook Salmon [J]. J Hered, 2025.
[15]SHASHKOVA T I, GOREV D D, PAKHOMOV E D, et al. The GWAS-MAP platform for aggregation of results of genome-wide association studies and the GWAS-MAP|homo database of 70 billion genetic associations of human traits [J]. Vavilovskii Zhurnal Genet Selektsii, 2020, 24(8): 876-84.
[16]BECK T, SHORTER T, BROOKES A J. GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies [J]. Nucleic Acids Res, 2020, 48(D1): D933-d40.
[17]The Genotype-Tissue Expression (GTEx) project [J]. Nat Genet, 2013, 45(6): 580-5.
[18]VON MERING C, HUYNEN M, JAEGGI D, et al. STRING: a database of predicted functional associations between proteins [J]. Nucleic Acids Res, 2003, 31(1): 258-61.
[19]FAROOQ Q U A, SHAUKAT Z, AIMAN S, LI C H. Protein-protein interactions: Methods, databases, and applications in virus-host study [J]. World J Virol, 2021, 10(6): 288-300.
[20]LITTLE M P, BOERMA M, BERNIER M O, et al. Effects of confounding and effect-modifying lifestyle, environmental and medical factors on risk of radiation-associated cardiovascular disease [J]. BMC Public Health, 2024, 24(1): 1601.
[21]AIN Q U, SARFRAZ M, PRASESTI G K, et al. Confounders in Identification and Analysis of Inflammatory Biomarkers in Cardiovascular Diseases [J]. Biomolecules, 2021, 11(10).
[22]吴含, 李长清. 孟德尔随机化在神经病学研究中的应用进展 [J]. 临床医学进展, 2024, 14(7): 380-8.
[23]YU X, CHEN Y, LEI L, et al. Mendelian randomization analysis of blood metabolites and immune cell mediators in relation to GVHD and relapse [J].
[24]BAO X, LIANG Y, CHANG H, et al. Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside [J].
[25]CHAPMAN M J, STOCK J K, GINSBERG H N. PCSK9 inhibitors and cardiovascular disease: heralding a new therapeutic era [J]. Curr Opin Lipidol, 2015, 26(6): 511-20.
[26]WATTS G F, SCHWABE C, SCOTT R, et al. RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts [J].
[27]GOBEIL É, BOURGAULT J, MITCHELL P L, et al. Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk [J]. Eur Heart J, 2024, 45(9): 707-21.
[28]GUSAROVA V, ALEXA C A, WANG Y, et al. ANGPTL3 blockade with a human monoclonal antibody reduces plasma lipids in dyslipidemic mice and monkeys [J]. J Lipid Res, 2015, 56(7): 1308-17.
[29]MERCANOGLU B, WASCHKOWSKI S-A, NEUBURG E, et al. GalNT2-mediated O-glycosylation affects pancreas development and function in mice [J].
[30]DI PAOLA R, MARUCCI A, MANGIACOTTI D, et al. Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia [J]. Adv Biol (Weinh), 2023, 7(9): e2200319.
[31]MAZHAR F, FAUCON A L, FU E L, et al. Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease [J]. Eur Heart J, 2024, 45(44): 4719-30.
[32]MEHTA N N, DEGOMA E, SHAPIRO M D. IL-6 and Cardiovascular Risk: A Narrative Review [J]. Curr Atheroscler Rep, 2024, 27(1): 12.
[33]GAMA A P, SANTOS I S, OLMOS R D, et al. C-reactive protein as an inflammatory marker of acute infections outside intensive care settings: case report and evidence-based literature review [J].Autops Case Rep, 2011, 1(4): 3-9.
[34]ARROYO-ESPLIGUERO R, VIANA-LLAMAS M C, SILVA-OBREGóN A, AVANZAS P. The Role of C-reactive Protein in Patient Risk Stratification and Treatment [J]. Eur Cardiol, 2021, 16:e28.
[35]杨懿,高新,宋海峰.GLP-1受体激动剂的临床研究进展[J].中国新药杂志,2015,24(19):6.
[36]MAHAPATRO A, BOZORGI A, OBULAREDDY S U J, et al. Glucagon-like peptide-1 agonists in cardiovascular diseases: a bibliometric analysis from inception to 2023 [J]. Ann Med Surg (Lond), 2024, 86(11): 6602-18.
[37]SEVILLA-GONZáLEZ M, SMITH K, WANG N, et al. Heterogeneous effects of genetic variants and traits associated with fasting insulin on cardiometabolic outcomes [J].
[38]张婧,魏志梁,王云立, 孙守刚. 心肌纤维化发病机制研究进展[J].中国循证心血管医学杂志,2024,16(2):253-6.
[39]CHAI T, WANG Z, YANG X, et al. PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels [J].Front Cardiovasc Med, 2022, 9: 763015.
[40]HOUSHMAND G, ALEMZADEH-ANSARI M J, MAZLOUMZADEH S, et al. Polymorphism of rs599839 in the PSRC1 gene is associated with coronary artery disease in an Iranian population [J].J Cardiovasc Thorac Res,2023,15(3):168-73.