RESUMO
BACKGROUND AND PURPOSE: A locus containing the elastin gene has been linked to familial intracranial aneurysms in 2 distinct populations. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes of SNPs in the elastin gene with the occurrence of subarachnoid hemorrhage (SAH) from sporadic aneurysms in the Netherlands. METHODS: We genotyped 167 SAH patients and 167 matching controls for 18 exonic and intronic SNPs in the elastin gene. A Bonferroni correction was applied for multiple comparisons with all novel associations, with a correction factor derived from the number of SNPs tested (P value after Bonferroni correction [P(corr)]). RESULTS: SAH was statistically significant associated with an SNP in exon 22 of the elastin gene (minor allele frequency was 0.000 in patients and 0.028 in controls; odds ratio [OR], 0.0; 95% CI, 0.0 to 0.7; P=0.004; P(corr)=0.05) and possibly with an SNP in intron 5 (minor allele frequency was 0.062 in patients and 0.128 in controls; OR, 0.5; 95% CI, 0.2 to 0.8; P=0.007; P(corr)=0.08). Haplotypes of intron 5/exon 22 (P(corr)=0.002), intron 4/exon 22 (P(corr)=0.02), and intron 4/intron 5/exon 22 (P=9.0x10(-9)) were also associated with aneurysmal SAH. CONCLUSIONS: Variants and haplotypes within the elastin gene are associated with the risk of sporadic SAH in Dutch patients. Gradual increase of statistical power with the inclusion of 2 or 3 SNPs in the studied haplotypes supports the validity of our conclusion that the elastin gene is a susceptibility locus for SAH.
