Association Analysis of Genes Involved in the Maintenance of the Integrity of the Extracellular Matrix with Intracranial Aneurysms in a Japanese Cohort

An association between versican (CSPG2), perlecan (HSPG2), fibrillin 2 (FBN2) and collagen 4A1 (COL4A1) gene variants and intracranial aneurysms (IA) has been reported in 2 studies analyzing Dutch IA patients. The aim of this study was to verify these associations in a Japanese IA population. In addition, a meta-analysis on the association of these genes and IA for the combined Dutch and Japanese populations was performed.The associated single nucleotide polymorphisms (SNPs) in these genes identified in the Dutch study were genotyped in 632 Japanese IA patients and 808 healthy control subjects using TaqMan SNP genotyping assays.A similar association to that previously found in the Dutch population was found for the CSPG2 (rs251124) and HSPG2 (rs3767137) SNPs, although both associations were not statistically significant in the Japanese population (CSPG2 OR 1.18, 95% CI 0.98-1.41, p = 0.08; HSPG2 OR 1.09, 95% CI 0.90-1.32). Combining the Dutch and Japanese data for a meta-analysis showed an overall association between the CSPG2 SNP and IA (OR 1.29, 95% CI 1.12-1.48, p = 0.0005) and the HSPG2 SNP and IA (OR 1.22, 95% CI 1.08-1.39, p = 0.002). No differences in SNP frequency were observed for FBN2 and COL4A1 between Japanese patients and controls.By analyzing HSPG2, CSPG2, FBN2 and COL4A1, we were able to replicate the association of CSPG2 and show that there is a trend for HSPG2 towards association in the Japanese IA population by means of a meta-analysis combining the Dutch and Japanese results. The association of FBN2 and COL4A1 could not be replicated in the Japanese IA population.