ARHGEF7遗传变异与颅内动脉瘤相关

doi:10.16352/j.issn.1001-6325.2023.04.0576

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (4): 576-582.doi: 10.16352/j.issn.1001-6325.2023.04.0576

ARHGEF7遗传变异与颅内动脉瘤相关

吴毅毅^1,2, 张梅^1*, 杨云云³, 李亚强¹, 李静¹, 贺佳乐¹, 张伟丽²

1.安徽理工大学第一附属医院(淮南市第一人民医院) 神经内科,安徽淮南 232000;
2.中国医学科学院北京协和医学院国家心血管病中心阜外医院心血管疾病国家重点实验室,国家心血管病临床医学研究中心,北京 100037;
3.厦门大学第一附属医院临床实验室基因检测重点实验室,福建厦门 361000

收稿日期:2022-12-21 修回日期:2023-02-16 出版日期:2023-04-05 发布日期:2023-04-03
通讯作者: ^*hnzhangmei2008@163.com
基金资助:
国家自然科学基金(81670038,91339101);安徽省科技攻关项目(12010402124);安徽省职业健康安全工程实验室开放课题基金(AYZJSGCLK202202003)

Association of ARHGEF7 genetic variants with intracranial aneurysm

WU Yiyi^1,2, ZHANG Mei^1*, YANG Yunyun³, LI Yaqiang¹, LI Jing¹, HE Jiale¹, ZHANG Weili²

1. Department of Neurology, the First Affiliated Hospital of Anhui University of Science and Technology (the First People's Hospital of Huainan), Huainan 232000;
2. National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, CAMS & PUMC, Beijing 100037;
3. Clinical Laboratory, Key Laboratory of Genetic Testing, the First Affiliated Hospital of Xiamen University, Xiamen 361000, China

Received:2022-12-21 Revised:2023-02-16 Online:2023-04-05 Published:2023-04-03
Contact: ^*hnzhangmei2008@163.com

摘要/Abstract

摘要： 目的探讨Rho鸟嘌呤核苷酸交换因子7(ARHGEF7)基因遗传变异与颅内动脉瘤形成和破裂风险的关系。方法收集颅内动脉瘤患者121例(包括未破裂组患者41例,破裂组患者80例)和健康对照155名,检测ARHGEF7的10个遗传变异。利用logistic回归模型分析ARHGEF7遗传变异与颅内动脉瘤发生和破裂风险的关系。结果在校正年龄、性别和传统心血管危险因素后,与rs4145274GG基因型相比,rs4145274GA与颅内动脉瘤破裂风险降低相关,比值比为0.24[95%可信区间(CI):0.09～0.69,P＜0.05]; 与rs1555751CC基因型相比,rs1555751CT与颅内动脉瘤破裂风险降低也相关,比值比为0.17(95% CI:0.05～0.63,P＜0.05)。rs4145274和rs1555751的联合效应提示患者遗传风险评分越高,颅内动脉瘤破裂风险越低,比值比为0.14(95% CI:0.04～0.55,P＜0.05)。结论 ARHGEF7遗传变异可能是颅内动脉瘤破裂风险的遗传标记。

关键词: Rho鸟嘌呤核苷酸交换因子7, 遗传变异, 颅内动脉瘤, 疾病风险

Abstract: Objective To identify the relationship between Rho guanine nucleotide exchange factor 7 (ARHGEF7) genetic variants and the formation and rupture risk of intracranial aneurysms. Methods Ten variants of the ARHGEF7 were detected in a case-control study which included 121 patients with intracranial aneurysms (including 41 unruptured and 80 ruptured patients) and 155 healthy controls. The relationship between variants and occurrence and rupture risk of intracranial aneurysms was examined by multivariate logistic regression model. Results After adjustment for age, sex, and traditional cardiovascular risk factors, the rs4145274GA genotype was associated with a decreased rupture risk of intracranial aneurysms as compared with rs4145274GG genotype, and odds ratio was 0.24[95% confidence interval (CI):0.09~0.69, P＜0.05]. The rs1555751CT genotype was also associated with a decreased rupture risk of intracranial aneurysms as compared with rs1555751CC genotype, and odds ratio was 0.17(95% CI: 0.05~0.63, P＜0.05). The combined effect rs4145274 and rs1555751 suggested that the patients with an increased genetic risk score had a lower rupture risk of intracranial aneurysms, and the odds ratio was 0.14(95% CI: 0.04~0.55, P＜0.05). Conclusions The study indicates that ARHGEF7 genetic variants potentially serve as potential genetic markers for the risk evaluation of ruptured intracranial aneurysms.

Key words: Rho guanine nucleotide exchange factor 7 (ARHGEF7), genetic variants, intracranial aneurysm, disease risk

中图分类号:

R743.3

吴毅毅, 张梅, 杨云云, 李亚强, 李静, 贺佳乐, 张伟丽. ARHGEF7遗传变异与颅内动脉瘤相关[J]. 基础医学与临床, 2023, 43(4): 576-582.

WU Yiyi, ZHANG Mei, YANG Yunyun, LI Yaqiang, LI Jing, HE Jiale, ZHANG Weili. Association of ARHGEF7 genetic variants with intracranial aneurysm[J]. Basic & Clinical Medicine, 2023, 43(4): 576-582.

参考文献 14

[1]	Vernooij MW, Ikram MA, Tanghe HL. Incidental findings on brain MRI in the general population[J]. N Engl J Med, 2007, 357:1821-1828.
[2]	Etminan N, Rinkel GJ. Unruptured intracranial aneurysms:development, rupture and preventive management[J]. Nat Rev Neurol, 2016, 12:699-713.
[3]	Caranci F, Briganti F, Cirillo L, et al. Epidemiology and genetics of intracranial aneurysms[J]. Eur J Radiol, 2013, 82:1598-1605.
[4]	孔祥溢, 关健, 李军, 等. 氧化应激促发颅内动脉瘤的研究进展 [J]. 基础医学与临床, 2015, 35:558-562.
[5]	Birukova AA, Malyukova I, Mikaelyan A, et al. Tiam1 and beta-pix mediate rac-dependent endothelial barrier protective response to oxidized phospholipids[J]. J Cell Physiol, 2007, 211:608-617.
[6]	Yang R, Zhang Y, Huang D, et al. Miconazole protects blood vessels from MMP9-dependent rupture and hemorrhage[J]. Dis Model Mech, 2017, 10:337-348.
[7]	Liu J, Fraser SD, Faloon PW, et al. A beta-pix pak2a signaling pathway regulates cerebral vascular stability in zebrafish[J]. Proc Natl Acad Sci U S A, 2007, 104:13990-13995.
[8]	Gabriel S, Ziaugra L, Tabbaa D. SNP genotyping using the sequenom massarray iplex platform[J]. Curr Protoc Hum Genet, 2009, 2:2-12.
[9]	Smeland OB, Frei O, Shadrin A, et al. Discovery of shared genomic loci using the conditional false discovery rate approach[J]. Hum Genet, 2020, 139:85-94.
[10]	Omelchenko T, Rabadan MA, Hernandez-Martinez R, et al. Beta-pix directs collective migration of anterior visceral endoderm cells in the early mouse embryo[J]. Genes Dev, 2014, 28:2764-2777.
[11]	Liu J, Zeng L, Kennedy RM, et al. Beta-pix plays a dual role in cerebral vascular stability and angiogenesis, and interacts with integrin alphavbeta8[J]. Dev Biol, 2012, 363:95-105.
[12]	Zheng S, Su A, Sun H, et al. The association between interleukin-6 gene polymorphisms and intracranial aneurysms: a Meta-analysis[J]. Hum Immunol, 2013, 74:1679-1683.
[13]	Yang S, Wang T, You C, et al. Association of polymorphisms in the elastin gene with sporadic ruptured intracranial aneurysms and unruptured intracranial aneurysms in Chinese patients[J]. Int J Neurosci, 2013, 123:454-458.
[14]	Bakker MK, van der Spek RAA, van Rheenen W, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors[J]. Nat Genet, 2020, 52:1303-1313.

ARHGEF7遗传变异与颅内动脉瘤相关

Association of ARHGEF7 genetic variants with intracranial aneurysm

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