The Association between Genes Polymorphisms of Heparan Sulfate Proteoglycan 2 (HSPG2) and Chondroitin Sulfate Proteoglycan 2 (CSPG2) and Intracranial Aneurysm Susceptibil-ity: A Meta-Analysis
Background: We aimed to investigate whether the polymorphisms of gene heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) are associated with increased risk of intracranial aneurysms (IAs) susceptibility.
Methods: The Cochrane Library, Medline, PubMed, and Embase databases were carefully searched for potential researches before Mar 30, 2018. The title, abstract, and full text were assessed to determine whether the paper was suitable for inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between CSPG2 and HSPG2 polymorphisms and IAs susceptibility.
Results: We enrolled 7 papers, 4 matched single nucleotide polymorphisms (SNPs) of CSPG2 (rs173686, rs251124) or HSPG2 (rs173686, rs251124), and a total of 8651 participations (3674 with IAs and 4977 for control). For the rs251124 polymorphism of CSPG2, the quantitative synthesis from 5 studies showed significant difference in the gene allele comparison of T vs. C (OR, 1.129; 95% CI, 1.029, 1.238; P=0.01). Similar results were found for rs3767137 of HSPG2 (A vs. G, OR, 0.842, 95% CI=0.759-0.935, P=0.001). However, for the rs173686 polymorphism of CSPG2 and rs7556412 polymorphism of HSPG2, no significant difference was found (P=0.259 and P=0.474, respectively)
Conclusion: The SNPs rs251124 of CSPG2 and rs3767137 of HSPG2 had statistically significant associations with IAs susceptibility. The minor allele T of rs251124 demonstrated a harmful effect but the minor allele A of rs3767137 demonstrated a protective role with regard to the risk of IAs. However, no such associations were found in the SNPs rs173686 of CSPG2 and rs7556412 of HSPG2.
2. Zholdybayeva EV, Medetov YZ, Aitkulova AM, et al (2018). Genetic Risk Factors for Intracranial Aneurysm in the Kazakh Population. J Mol Neurosci, 66(1):135-145.
3. White AC, Kumpe DA, Roark CD, et al (2018). Patterns, Predictors, and Out-comes of Post Procedure Delayed Hem-orrhage Following Flow Diversion for Intracranial Aneurysm Treatment. World Neurosurg, 115:e97-e104.
4. Can A, Castro VM, Dligach D, et al (2018). Lipid-Lowering Agents and High HDL (High-Density Lipoprotein) Are Inversely Associated With Intracranial Aneurysm Rupture. Stroke, 49(5):1148-1154.
5. Zhou S, Gan-Or Z, Ambalavanan A, et al (2018). Genome-wide association analysis identifies new candidate risk loci for fa-milial intracranial aneurysm in the French-Canadian population. Sci Rep, 8(1):4356.
6. Cho SM, Marquardt RJ, Rice CJ, et al (2018). Cerebral Microbleeds Predict Infectious Intracranial Aneurysm in Infective Endo-carditis. Eur J Neurol, 25(7):970-975.
7. Chen Y, Zhang Y, Chao YJ, et al (2017). Stent-assisted coiling embolization of middle cerebral artery trifurcation wide-necked aneurysms. Eur Rev Med Pharmacol Sci, 21(19):4346-4349.
8. Feigin VL, Rinkel GJE, Lawes CMM, et al (2005). Risk Factors for Subarachnoid Hemorrhage. An Updated Systematic Re-view of Epidemiological Studies. Stroke, 36(12):2773-2780.
9. Krischek B, Inoue I (2006). The genetics of intracranial aneurysms. J Hum Genet, 51(7):587-94.
10. Ruigrok YM, Rinkel GJ, Van'T SR, et al (2006). Evidence in favor of the contribu-tion of genes involved in the mainte-nance of the extracellular matrix of the ar-terial wall to the development of intracra-nial aneurysms. Hum Mol Genet, 15(22):3361-8.
11. Ruigrok YM, Rinkel GJ (2008). Genetics of intracranial aneurysms. Stroke, 39(3):1049-55.
12. Ruigrok YM, Rinkel GJ, Wijmenga C (2006). The versican gene and the risk of intra-cranial aneurysms. Stroke, 37(9): 2372-2374.
13. Kuboyama K, Tanga N, Suzuki R, et al (2017). Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation. PLoS One, 12(12):e0189164.
14. Ruigrok YM, Rinkel GJ, Wijmenga C, et al (2009). Association analysis of genes in-volved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort. Cerebro-vasc Dis, 28(2):131-4.
15. Sun H, Zhang D, Zhao J (2007). Chon-droitin sulfate proteoglycan 2 (CSPG2) gene polymorphisms rs173686 and rs251124 are not associated with intra-cranial aneurysms in Chinese Han na-tionality. Ups J Med Sci, 112(3):289-295.
16. Zhu X, Shi Y, Lu F, et al (2013). Association of single nucleotide polymorphisms of CSPG2 and HSPG2 genes with intracra-nial aneurysm in ethnic Han Chinese population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 30(2):218-221.
17. Chang MY, Kang I, Gale M Jr, et al (2017). Versican is produced by Trif- and type I interferon-dependent signaling in macro-phages and contributes to fine control of innate immunity in lungs. Am J Physiol Lung Cell Mol Physiol, 313(6):L1069-L1086.
18. Theocharis AD, Tsolakis I, Hjerpe A, et al (2001). Human abdominal aortic aneu-rysm is characterized by decreased versi-can concentration and specific down-regulation of versican isoform V(0). Ath-erosclerosis, 154(2):367-376.
19. Tang F, Lord MS, Stallcup WB, et al (2018). Cell surface chondroitin sulphate proteo-glycan 4 (CSPG4) binds to the basement membrane heparan sulphate proteogly-can, perlecan, and is involved in cell ad-hesion. J Biochem, 163(5):399-412.