| Citation: |
HAN Xiuyan, XU Hua, ZHANG Qinli. Causal relationship between serum uric acid level and cerebrovascular disease: a two-sample bidirectional Mendelian randomization study[J]. Journal of Clinical Medicine in Practice, 2025, 29(1): 66-72. DOI: 10.7619/jcmp.20243219
|
To evaluate the causal relationship between serum uric acid (SUA) level and cerebrovascular disease (CVD) by a two-sample bidirectional Mendelian randomization (MR) study.
Single nucleotide polymorphisms (SNPs) from Genome-Wide Association Studies (GWAS) were obtained as instrumental variables for both samples. Inverse-variance weighted (IVW) method was primarily adopted, with weighted median method, weighted mode method, and MR-Egger regression serving as supplementary approaches for sensitivity analyses to verify the robustness of the results.
The forward IVW analysis results showed that increased SUA was a risk factor for stroke (OR=1.183, 95% CI, 1.081 to 1.295, P=2.51×10-4), ischemic stroke (OR=1.196, 95% CI, 1.084 to 1.320, P=3.81×10-4), and large artery atherosclerotic stroke (OR=1.466, 95% CI, 1.134 to 1.897, P=0.004), and also a protective factor for vascular dementia (OR=0.451, 95% CI, 0.273 to 0.745, P=0.002) and multi-infarct dementia (OR=0.372, 95% CI, 0.144 to 0.959, P=0.041). The reverse IVW analysis results did not support a causal effect of genetically predicted CVD risk on SUA level. All significant results were corrected by Bonferroni with P value less than 0.005. Sensitivity analyses further confirmed the reliability of the study findings.
The MR analysis reveals positive correlations between increased SUA level and the risk of stroke, ischemic stroke and large artery atherosclerotic stroke, and negative correlations of SUA level with the risk of vascular dementia and multi-infarct dementia.
| [1] |
GOLDSTEIN L B. Introduction for focused updates in cerebrovascular disease[J]. Stroke, 2020, 51(3): 708-710. doi: 10.1161/STROKEAHA.119.024159
|
| [2] |
GBD Lifetime Risk of Stroke Collaborators, FEIGIN V L, NGUYEN G, et al. Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016[J]. N Engl J Med, 2018, 379(25): 2429-2437. doi: 10.1056/NEJMoa1804492
|
| [3] |
WANG Q W, WEN X, KONG J M. Recent progress on uric acid detection: a review[J]. Crit Rev Anal Chem, 2020, 50(4): 359-375. doi: 10.1080/10408347.2019.1637711
|
| [4] |
CORTESE F, SCICCHITANO P, CORTESE A M, et al. Uric acid in metabolic and cerebrovascular disorders: a review[J]. Curr Vasc Pharmacol, 2020, 18(6): 610-618. doi: 10.2174/1570161118666191217123930
|
| [5] |
DU L, MA J H, ZHANG X N. Higher serum uric acid may contribute to cerebral infarction in patients with type 2 diabetes mellitus: a meta-analysis[J]. J Mol Neurosci, 2017, 61(1): 25-31. doi: 10.1007/s12031-016-0848-y
|
| [6] |
ZHONG C K, ZHONG X Y, XU T, et al. Sex-specific relationship between serum uric acid and risk of stroke: a dose-response meta-analysis of prospective studies[J]. J Am Heart Assoc, 2017, 6(4): e005042. doi: 10.1161/JAHA.116.005042
|
| [7] |
ZHANG P, WANG R, QU Y, et al. Serum uric acid levels and outcome of acute ischemic stroke: a dose-response meta-analysis[J]. Mol Neurobiol, 2024, 61(3): 1704-1713. doi: 10.1007/s12035-023-03634-y
|
| [8] |
TANA C, TICINESI A, PRATI B, et al. Uric acid and cognitive function in older individuals[J]. Nutrients, 2018, 10(8): 975. doi: 10.3390/nu10080975
|
| [9] |
LATOURTE A, SOUMARÉ A, BARDIN T, et al. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study[J]. Ann Rheum Dis, 2018, 77(3): 328-335. doi: 10.1136/annrheumdis-2016-210767
|
| [10] |
LI Q, CEN K W, CUI Y, et al. Uric acid levels and their association with vascular dementia and Parkinson's disease dementia: a meta-analysis[J]. Neurol Sci, 2023, 44(6): 2017-2024. doi: 10.1007/s10072-023-06620-3
|
| [11] |
NAZARZADEH M, PINHO-GOMES A C, BIDEL Z, et al. Plasma lipids and risk of aortic valve stenosis: a Mendelian randomization study[J]. Eur Heart J, 2020, 41(40): 3913-3920. doi: 10.1093/eurheartj/ehaa070
|
| [12] |
LAWLOR D A, HARBORD R M, STERNE J A C, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology[J]. Stat Med, 2008, 27(8): 1133-1163. doi: 10.1002/sim.3034
|
| [13] |
CLAYTON G L, GONÇALVES A, SOARES, et al. A framework for assessing selection and misclassification bias in Mendelian randomisation studies: an illustrative example between body mass index and covid-19[J]. BMJ, 2023, 381: e072148. http://www.semanticscholar.org/paper/0f8c69006e263a539eaca48de55c0325fc24e210
|
| [14] |
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[J]. BMJ, 2021, 375: n2233. http://www.xueshufan.com/publication/3210406414
|
| [15] |
LU N, DUBREUIL M, ZHANG Y Q, et al. Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study[J]. Ann Rheum Dis, 2016, 75(3): 547-551. doi: 10.1136/annrheumdis-2014-206917
|
| [16] |
SEKULA P, FABIOLA GRECO M, PATTARO C, et al. Mendelian randomization as an approach to assess causality using observational data[J]. J Am Soc Nephrol, 2016, 27(11): 3253-3265. doi: 10.1681/ASN.2016010098
|
| [17] |
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. doi: 10.1001/jama.2021.18236
|
| [18] |
刘波, 游俊杰, 郑思琳, 等. 基于孟德尔随机化分析胃食管反流病与慢性阻塞性肺疾病的因果关系研究[J]. 实用临床医药杂志, 2024, 28(1): 113-117.
|
| [19] |
SAKAUE S, KANAI M, TANIGAWA Y, et al. A cross-population atlas of genetic associations for 220 human phenotypes[J]. Nat Genet, 2021, 53(10): 1415-1424. doi: 10.1038/s41588-021-00931-x
|
| [20] |
MALIK R, CHAUHAN G, TRAYLOR M, et al. Multiancestry genome-wide association study of 520, 000 subjects identifies 32 loci associated with stroke and stroke subtypes[J]. Nat Genet, 2018, 50(4): 524-537. doi: 10.1038/s41588-018-0058-3
|
| [21] |
张卫娜, 郑丽, 刘德平. 尿酸与心房颤动、冠心病和充血性心力衰竭因果关联的两样本孟德尔随机化研究[J]. 中国心血管杂志, 2023, 28(5): 423-429. doi: 10.3969/j.issn.1007-5410.2023.05.004
|
| [22] |
BURGESS S, THOMPSON S G, CRP CHD GENETICS COLLABORATION. Avoiding bias from weak instruments in Mendelian randomization studies[J]. Int J Epidemiol, 2011, 40(3): 755-764. doi: 10.1093/ije/dyr036
|
| [23] |
李威, 柴金莲, 贾海峰, 等. 微量营养素与骨坏死的因果关系: 来自双向孟德尔随机试验的证据[J]. 中国组织工程研究, 2024, 33(33): 5308-5314. doi: 10.12307/2024.686
|
| [24] |
HEMANI G, TILLING K, DAVEY SMITH G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data[J]. PLoS Genet, 2017, 13(11): e1007081. doi: 10.1371/journal.pgen.1007081
|
| [25] |
SUI X H, LIU T T, LIANG Y, et al. Psychiatric disorders and cardiovascular diseases: a Mendelian randomization study[J]. Heliyon, 2023, 9(10): e20754. doi: 10.1016/j.heliyon.2023.e20754
|
| [26] |
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. doi: 10.1038/s41588-018-0099-7
|
| [27] |
BOWDEN J, DAVEY SMITH G, BURGESS S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression[J]. Int J Epidemiol, 2015, 44(2): 512-525. doi: 10.1093/ije/dyv080
|
| [28] |
HEMANI G, ZHENG J, ELSWORTH B, et al. The MR-Base platform supports systematic causal inference across the human phenome[J]. Elife, 2018, 7: e34408. doi: 10.7554/eLife.34408
|
| [29] |
LI M, HOU W S, ZHANG X W, et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies[J]. Atherosclerosis, 2014, 232(2): 265-270. doi: 10.1016/j.atherosclerosis.2013.11.051
|
| [30] |
WANG C Q, GAO Y K, SMERIN D, et al. Genetically predicted type 2 diabetes mellitus mediates the causal association between plasma uric acid and ischemic stroke[J]. Int Immunopharmacol, 2024, 134: 112267. doi: 10.1016/j.intimp.2024.112267
|
| [31] |
黎启娇, 萨仁, 林智鹏, 等. 补髓通窍益脑汤联合靳三针治疗血管性痴呆患者的效果观察[J]. 实用临床医药杂志, 2022, 26(14): 46-49, 54. doi: 10.7619/jcmp.20214795
|
| [32] |
HONG J Y, LAN T Y, TANG G J, et al. Gout and the risk of dementia: a nationwide population-based cohort study[J]. Arthritis Res Ther, 2015, 17(1): 139. doi: 10.1186/s13075-015-0642-1
|
| [33] |
XU Y Z, WANG Q, CUI R T, et al. Uric acid is associated with vascular dementia in Chinese population[J]. Brain Behav, 2017, 7(2): e00617. doi: 10.1002/brb3.617
|
| [34] |
CHEN T S, MI N N, LAO H Y, et al. Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study[J]. BMC Med, 2024, 22(1): 115. doi: 10.1186/s12916-024-03302-5
|
| [35] |
SÁNCHEZ-LOZADA L G, TAPIA E, SANTAMARÍA J, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats[J]. Kidney Int, 2005, 67(1): 237-247. doi: 10.1111/j.1523-1755.2005.00074.x
|
| [36] |
SO A, THORENS B. Uric acid transport and disease[J]. J Clin Invest, 2010, 120(6): 1791-1799. doi: 10.1172/JCI42344
|
| [37] |
CRIŞAN T O, CLEOPHAS M C, OOSTING M, et al. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra[J]. Ann Rheum Dis, 2016, 75(4): 755-762. doi: 10.1136/annrheumdis-2014-206564
|
| [38] |
CRIŞAN T O, CLEOPHAS M C P, NOVAKOVIC B, et al. Uric acid priming in human monocytes is driven by the AKT-PRAS40 autophagy pathway[J]. Proc Natl Acad Sci U S A, 2017, 114(21): 5485-5490. doi: 10.1073/pnas.1620910114
|
| [39] |
KOMAKI Y, SUGIURA H, KOARAI A, et al. Cytokine-mediated xanthine oxidase upregulation in chronic obstructive pulmonary disease's airways[J]. Pulm Pharmacol Ther, 2005, 18(4): 297-302. doi: 10.1016/j.pupt.2005.01.002
|
| [40] |
CHERUBINI A, POLIDORI M C, BREGNOCCHI M, et al. Antioxidant profile and early outcome in stroke patients[J]. Stroke, 2000, 31(10): 2295-2300. doi: 10.1161/01.STR.31.10.2295
|
| [41] |
BROUNS R, WAUTERS A, VAN DE VIJVER G, et al. Decrease in uric acid in acute ischemic stroke correlates with stroke severity, evolution and outcome[J]. Clin Chem Lab Med, 2010, 48(3): 383-390. doi: 10.1515/CCLM.2010.065
|
| [1] | LI Panying, ZHANG Xiaofeng, YIN Jianyun, REN Xiaowei, YANG Jing, NI Qian. Research progress on genetic factors related to lung function[J]. Journal of Clinical Medicine in Practice, 2025, 29(3): 133-137, 143. DOI: 10.7619/jcmp.20244444 |
| [2] | DONG Kui, WU Jie, YAN Jing, LIU Haitao, QIAO Guan'en. Mendelian randomization study on the causality between dietary factors and gastroesophageal reflux disease[J]. Journal of Clinical Medicine in Practice, 2024, 28(23): 75-80, 86. DOI: 10.7619/jcmp.20242711 |
| [3] | ZHANG Kaiyue, WEI Lai, HUANG Yuanpeng. Visual analysis of the knowledge map of Mendelian randomization studies in the field of cancer based on CiteSpace software[J]. Journal of Clinical Medicine in Practice, 2024, 28(23): 1-7. DOI: 10.7619/jcmp.20243021 |
| [4] | ZHU Jingxin, MA Rui, CHAI Zekun, DONG Yuran, WANG Le. A Mendelian randomization study on the causal association between social stress and tinnitus onset[J]. Journal of Clinical Medicine in Practice, 2024, 28(19): 55-59, 67. DOI: 10.7619/jcmp.20242091 |
| [5] | LIU Lianlian, YU Huiyong, LI Lei, GUO Yufei, NIE Tianyang, MAN Tian, WEI Shixiang, XIE Chuxi, CHEN Tianyun, WANG Chengxiang. Mendelian randomization analysis of the causal association between bronchial asthma and bone mineral density[J]. Journal of Clinical Medicine in Practice, 2024, 28(14): 24-29. DOI: 10.7619/jcmp.20241383 |
| [6] | XU Minglu, YANG Xiaohan, LIU Qiannan, YI Chang. Analysis in association rules of chronic diseases in the elderly people[J]. Journal of Clinical Medicine in Practice, 2024, 28(13): 103-108. DOI: 10.7619/jcmp.20240556 |
| [7] | LIU Bo, YOU Junjie, ZHENG Silin, HUANG Min. Causal relationship between gastroesophageal reflux disease and chronic obstructive pulmonary disease based on Mendelian randomization analysis[J]. Journal of Clinical Medicine in Practice, 2024, 28(1): 113-117. DOI: 10.7619/jcmp.20232575 |
| [8] | YAO Junjie, QI Wei, ZHANG Xinxin, LIU Chang, PANG Tingting, LI Jiahui, SHANG Qiangqiang. Research progress in diagnosis and treatment of lumbar spinal stenosis[J]. Journal of Clinical Medicine in Practice, 2022, 26(4): 136-140, 145. DOI: 10.7619/jcmp.20214841 |
| [9] | ZHANG Zeyuan, YANG Hongren. Effect of modified yinqiao powdeRon whole genome spectral expression in monkey with hand-foot-mouth disease induced by CA16 virus[J]. Journal of Clinical Medicine in Practice, 2017, (9): 126-128. DOI: 10.7619/jcmp.201709033 |
| [10] | CHEN Li-juan, LI Jian-yong, Qian Si-xuan, Qian Yu-jie, Xu Jia-ren, QIU Hai-rong. APPLICATION OF COMPARATIVE GENOMIC HYBRIDIZATION IN LYMPHOMA[J]. Journal of Clinical Medicine in Practice, 2006, (9): 1-3. DOI: 10.3969/j.issn.1672-2353.2006.09.001 |
© 2020 《实用临床医药杂志》编辑部
Address: 江苏省扬州市江阳中路136号，扬州大学江阳路北校区14号楼201室China Pos: 225009Tel: 0514-87978917、87978989、87978807
Supported by:
Beijing Renhe Information Technology Co., Ltd.
苏公网安备 32100302010246号
DownLoad: