Association of Kallikrein Gene Polymorphisms With Intracranial Aneurysms

Abstract

Background and Purpose-Genomewide

Aortic Aneurysms

“…Furthermore, both TAAD and AAA demonstrate genetic heterogeneity, as has been shown to be the case for yet another form of aneurysms, the intracranial aneurysms. 8 Elucidation of the genetic risk factors for aneurysmal diseases will require multidisciplinary approaches 9 ( Figure), in which animal studies, 4 although not discussed here, will play a key role.…”

Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms

“…6 Other loci of the linkage analyses in the Japanese population include 14q23, replicated by an association study. 7 In other ethnic groups, the perlecan gene (HSPG2) at 1p36.1-36.4, 8 the versican gene (CSPG2) at 5q14.3 9 and Kallikrein at 19q13 10 have been proposed as susceptibility genes for IA by case-control association study, among others.…”

Association analyses confirming a susceptibility locus for intracranial aneurysm at chromosome 14q23

“…Given a risk allele frequency of 0.2, a prevalence of 0.01 and a relative risk of 1.5, 240 cases and 240 controls are needed for an alpha of B0.05 with 80% power according to the Genetic Power Calculator (http://pngu.mgh.harvard.edu/*purcell/ gpc/), supposing that a marker allele is in complete LD with a disease allele. However, the relative risks of susceptibility genes for IA were less than 1.5 in most recent studies (Yoneyama et al 2004;Akagawa et al 2006;Inoue et al 2006;Ruigrok et al 2006aRuigrok et al , 2006bWeinsheimer et al 2007), and a marker allele is unlikely to be in complete LD with a disease allele because of the low coverage of SNP markers in theGeneChip 10 K mapping array. Thus, the power of the present study may not be sufficient to detect a relevant polymorphism for IA formation.…”

“…Linkage to 2p13 (Roos et al 2004) was shown in a large consanguineous family, but this finding has been retracted because newly diagnosed affected siblings did not show linkage to this locus (Ruigrok 2006). Among these nine linkage regions, the perlecan gene (HSPG2) at 1p36.1-36.4 (Ruigrok et al 2006a), the versican gene (CSPG2) at 5q14.3 (Ruigrok et al 2006b), elastin (ELN) and LIM domain kinase 1 (LIMK1) genes at 7q11 (Onda et al 2001;Akagawa et al 2006), collagen alpha 2(I) (COL1A2) at 7q22 (Yoneyama et al 2004), tumor necrosis factor receptor, superfamily member 13B (TNFRSF13B) at 17cen , and kallikrein at 19q13 (Weinsheimer et al 2007) have been proposed as susceptibility genes for IA. However, there has been a failure to replicate the linkage to 7q11 and the association of ELN polymorphisms with IA in several studies (Berthelemy-Okazaki et al 2005;Hofer et al 2003;Krex et al 2004;Mineharu et al 2006;Yamada et al 2003b), and linkage to 17cen also could not be replicated in a study of the same ethnic group .…”