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

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.

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.

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)

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.