Association of Polymorphisms and Haplotypes in the Elastin Gene in Dutch Patients With Sporadic Aneurysmal Subarachnoid Hemorrhage

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Abstract
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 =9.0×10 −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.