A genome-wide linkage and a haplotype association studies mapped intracranial aneurysm to elastin locus on chromosome 7

摘要

Intracranial aneurysm (IA) is a common disorder with a prevalence of 3-6% as shown by angiographic and autopsy studies and rupture of IA causes subarachnoid hemorrhage (SAH). It is well known that IA has a substantial genetic component, however, there has been little attention to the genetic determinants. We performed a genome-wide linkage study of IA in 104 Japanese affected sib-pairs using SIB PAL and GENEHUNTER programs. Evidence of linkage at chromosome 5q22-31 (MLS = 2.24), 7qll (MLS = 3.22), and 14q22 (MLS = 2.31) was found, The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for the disease. Fourteen distinct single nucleotide polymorphisms (SNPs) are identified in ELN, and no obvious allelic association between IA and each SNP was observed. A haplotype between the intron 20/23 polymorphism of ELN is strongly associated with IA (P=3.81 x 10~6), and homozygote patients are at high risk with an odds ratio of 4.39.