半乳糖凝集素1与动脉粥样硬化风险之间的因果关联:一项两样本孟德尔随机化研究
作者:
作者单位:

(1.新乡医学院第一附属医院,河南省卫辉市 453100;2.首都医科大学附属北京友谊医院心血管中心,北京市 100050)

作者简介:

崔瑞祥,硕士研究生,研究方向为心血管疾病诊治及预防,E-mail:crx6149@163.com。通信作者艾思志,博士,副教授,硕士研究生导师,研究方向为睡眠障碍与心血管疾病,E-mail:ai5542591@163.com。

基金项目:

国家自然科学基金项目(U1904159);中国科学技术协会青年人才托举工程项目(2021QNRC001)


Causal association between galectin-1 levels and the risk of atherosclerosis:a two-sample Mendelian randomization analysis
Author:
Affiliation:

1.The First Affiliated Hospital of Xinxiang Medical University,Weihui, Henan 453100, China;2.Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China)

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    摘要:

    目的]探讨遗传预测的半乳糖凝集素1(Gal-1)水平与动脉粥样硬化(As)之间的因果关联。 [方法]采用两样本孟德尔随机化(MR)研究方法,选择与Gal-1相关联的单核苷酸多态性(SNP)位点作为工具变量(IV),评估遗传预测的循环Gal-1水平与不同部位As风险的因果关联。 [结果]逆方差加权法(IVW)分析结果显示,经过Bonferroni校正后遗传预测的循环Gal-1水平与外周动脉粥样硬化及其他部位动脉粥样硬化(除外脑动脉、冠状动脉及外周动脉)的风险呈正相关(OR=1.6,5%CI:1.05~1.27,P=0.002;OR=1.16,95%CI:1.12~1.20,P=4.11E-17),而与冠状动脉粥样硬化和脑动脉粥样硬化发生风险均未发现存在因果关联的证据(OR=1.02,95%CI:0.91~1.14,P=0.765;OR=1.10,95%CI:0.94~1.29,P=0.220);在应用荟萃分析合并上述不同部位As的效应值后,遗传预测的循环Gal-1水平与As风险呈正相关(OR=1.12,95%CI:1.06~1.19)。 [结论]遗传预测的循环Gal-1水平与As的发病风险存在因果关联,Gal-1是预防As发生的潜在靶点。

    Abstract:

    Aim To explore the potential causal association between galectin-1 (Gal-1) levels and atherosclerosis (As). Methods Single nucleotide polymorphisms (SNP) associated with Gal-1 served as instrument variables (IV), and the causal association between genetically predicted Gal-1 levels and As was analyzed by the two-sample Mendelian randomization (MR) method. Results Inverse variance weighted (IVW) results showed that genetically predicted Gal-1 levels were positively associated with risk of peripheral As and other As type (excluding cerebral artery, coronary artery, and peripheral artery) after Bonferroni adjustment (OR=1.6,5%CI:1.05~1.27, P=0.002; OR=1.6,5%CI:1.12~1.20, P= 4.11E-17). There was no evidence supporting the causal association between Gal-1 and either coronary As or cerebral As (OR=1.2,5%CI:0.91~1.14, P=0.765; OR=1.0,5%CI:0.94~1.29, P=0.220); After Meta-analyzed the MR estimates of As outcomes at different sites, the results showed that genetically predicted Gal-1 levels were positively associated with As risk (OR=1.2,5%CI:1.06~1.19). ConclusionThe study suggests that genetically predicted Gal-1 level is causally associated with As risk, and Gal-1 is a potential target to prevent the occurrence of As.

    参考文献
    [1] GAO S C, XU L R, ZHANG Y L, et al.Salusin-α inhibits proliferation and migration of vascular smooth muscle cell via Akt/mTOR signaling.Cell Physiol Biochem, 8,0(5):1740-1753.
    [2] HERRINGTON W, LACEY B, SHERLIKER P, et al.Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease.Circ Res, 6,8(4):535-546.
    [3] LIBBY P, BURING J E, BADIMON L, et al.Atherosclerosis.Nat Rev Dis Primers, 9,5(1):56.
    [4] JEBARI B S, GALICIA G U, LARREA S A, et al.Pathophysiology of atherosclerosis.Int J Mol Sci, 2,3(6):3346.
    [5] BJRKEGREN J L M, LUSIS A J.Atherosclerosis:recent developments.Cell, 2,5(10):1630-1645.
    [6] MOISEEVA E P, JAVED Q, SPRING E L, et al.Galectin 1 is involved in vascular smooth muscle cell proliferation.Cardiovasc Res, 0,5(2):493-502.
    [7] RABINOVICH G A, BAUM L G, TINARI N, et al.Galectins and their ligands:amplifiers, silencers or tuners of the inflammatory response?.Trends Immunol, 2,3(6):313-320.
    [8] CHELLAN B, NARAYANI J, APPUKUTTAN P S.Galectin-1, an endogenous lectin produced by arterial cells, binds lipoprotein(a) [Lp(a)] in situ:relevance to atherogenesis.Exp Mol Pathol, 7,3(3):399-404.
    [9] HE X W, LI W L, LI C, et al.Serum levels of galectin-1, galectin-3, and galectin-9 are associated with large artery atherosclerotic stroke.Sci Rep, 7,7(1):40994.
    [10] CHOU R H, HUANG S S, KUO C S, et al.Galectin-1 is associated with the severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography.Sci Rep, 0,0(1):20683.
    [11] ROLDN-MONTERO R, PREZ-SEZ J M, CERRO-PARDO I, et al.Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm.Sci Adv, 2,8(11):eabm7322.
    [12] 王莉娜, ZHANG Zuofeng.孟德尔随机化法在因果推断中的应用.中华流行病学杂志, 7,8(4):547-552.WANG L N, ZHANG Z F.Mendelian randomization approach, used for causal inferences.Chin J Epidemiol, 7,8(4):547-552.
    [13] 林丽娟, 魏永越, 张汝阳, 等.孟德尔随机化方法在观察性研究因果推断中的应用.中华预防医学杂志, 9,3(6):619-624.LIN L J, WEI Y Y, ZHANG R Y, et al.Application of Mendelian randomization methods in causal inference of observational study.Chin J Prevent Med, 9,3(6):619-624.
    [14] DAVIES N M, HOLMES M V, DAVEY SMITH G.Reading mendelian randomisation studies:a guide, glossary, and checklist for clinicians.BMJ, 8,2:k601.
    [15] EMDIN C A, KHERA A V, KATHIRESAN S.Mendelian randomization.JAMA, 7,8(19):1925-1926.
    [16] PIERCE B L, BURGESS S.Efficient design for Mendelian randomization studies:subsample and 2-sample instrumental variable estimators.Am J Epidemiol, 3,8(7):1177-1184.
    [17] AI S Z, ZHANG J H, ZHAO G A, et al.Causal associations of short and long sleep durations with 12 cardiovascular diseases:linear and nonlinear Mendelian randomization analyses in UK Biobank.Eur Heart J, 1,2(34):3349-3357.
    [18] AI S Z, WANG X Y, WANG S S, et al.Effects of glycemic traits on left ventricular structure and function:a Mendelian randomization study.Cardiovasc Diabetol, 2,1(1):109.
    [19] SKRIVANKOVA V W, RICHMOND R C, WOOLF B A R, et al.Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR):explanation and elaboration.BMJ, 1,5:n2233.
    [20] HEMANI G, ZHENG J, ELSWORTH B, et al.The MR-base platform supports systematic causal inference across the human phenome.Elife, 8,7:e34408.
    [21] DRAKE I, FRYK E, STRINDBERG L, et al.The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease:evidence from cross-sectional, longitudinal and Mendelian randomisation analyses.Diabetologia, 2,5(1):128-139.
    [22] YANG J, FERREIRA T, MORRIS A P, et al.Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits.Nat Genet, 2,4(4):369-375, S1-3.
    [23] BURGESS S, BUTTERWORTH A, THOMPSON S G.Mendelian randomization analysis with multiple genetic variants using summarized data .Genet Epidemiol, 3,7(7):658-665.
    [24] BOWDEN J, DAVEY SMITH G, HAYCOCK P C, et al.Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator.Genet Epidemiol, 6,0(4):304-314.
    [25] 徐艺耘, 刘振球, 樊虹, 等.MR-Egger回归在孟德尔随机化分析中的应用.复旦学报(医学版), 1,8(6):804-809.XU Y Y, LIU Z Q, FAN H, et al.Application of MR-Egger regression in Mendelian randomization analysis.Fudan Univ J Med Sci, 1,8(6):804-809.
    [26] LEE C H, COOK S, LEE J S, et al.Comparison of two Meta-analysis methods:inverse-variance-weighted average and weighted sum of Z-scores.Genomics Inform, 6,4(4):173-180.
    [27] BOWDEN J, DAVEY SMITH G, BURGESS S.Mendelian randomization with invalid instruments:effect estimation and bias detection through Egger regression.Int J Epidemiol, 5,4(2):512-525.
    [28] BURGESS S, DAVEY SMITH G, DAVIES N M, et al.Guidelines for performing Mendelian randomization investigations.Wellcome Open Res, 9,4:186.
    [29] 王敏, 李瑾.炎性细胞在动脉粥样硬化中作用的研究进展.中国动脉硬化杂志, 2,0(3):265-270.WANG M, LI J.Progress on the role of inflammatory cells in atherosclerosis.Chin J Arterioscler, 2,0(3):265-270.
    [30] 肖素军, 赵明.动脉粥样硬化与免疫.中国动脉硬化杂志, 2,0(4):277-286.XIAO S J, ZHAO M.Atherosclerosis and immunity.Chin J Arterioscler, 2,0(4):277-286.
    [31] MALIK R K J, GHURYE R R, LAWRENCE-WATT D J, et al.Galectin-1 stimulates monocyte chemotaxis via the p44/42 MAP kinase pathway and a pertussis toxin-sensitive pathway.Glycobiology, 9,9(12):1402-1407.
    [32] GROOTAERT M O J, BENNETT M R.Vascular smooth muscle cells in atherosclerosis:time for a re-assessment.Cardiovasc Res, 1,7(11):2326-2339.
    [33] HUANG R, HUANG Y, ZENG G, et al.Ursodeoxycholic acid inhibits intimal hyperplasia, vascular smooth muscle cell excessive proliferation, migration via blocking miR-21/PTEN/AKT/mTOR signaling pathway.Cell Cycle, 0,9(8):918-932.
    [34] GABUNIA K, HERMAN A B, RAY M, et al.Induction of miR133a expression by IL-19 targets LDLRAP1 and reduces oxLDL uptake in VSMC.J Mol Cell Cardiol, 7,5:38-48.
    [35] ICHIKAWA T, UNOKI H, SUN H J, et al.Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human Apo(a) transgenic rabbits.Am J Pathol, 2,0(1):227-236.
    [36] AL-ANSARI S L, ZEEBREGTS C J, SLART R H J A, et al.Galectins in atherosclerotic disease.Trends Cardiovasc Med, 9,9(5):164-169.
    [37] DAV G, PATRONO C.Platelet activation and atherothrombosis.N Engl J Med, 7,7(24):2482-2494.
    [38] ROMANIUK M A, RABINOVICH G A, SCHATTNER M.Galectins in the regulation of platelet biology.Methods Mol Biol, 5,7:269-283.
    [39] FRY A, LITTLEJOHNS T J, SUDLOW C, et al.Comparison of sociodemographic and health-related characteristics of UK biobank participants with those of the general population.Am J Epidemiol, 7,6(9):1026-1034.
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崔瑞祥,王晓昱,左波,郭升,赵晨昊,徐艳敏,赵国安,艾思志.半乳糖凝集素1与动脉粥样硬化风险之间的因果关联:一项两样本孟德尔随机化研究[J].中国动脉硬化杂志,2023,31(5):419~426.

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  • 收稿日期:2022-07-13
  • 最后修改日期:2023-02-02
  • 在线发布日期: 2023-05-19