Confirmation of an Association of Single-Nucleotide Polymorphism rs1333040 on 9p21 With Familial and Sporadic Intracranial Aneurysms in Japanese Patients

被引：41

作者：

Hashikata, Hirokuni ^{[1
,2
,3
]}

Liu, Wanyang ^{[1
,2
]}

Inoue, Kayoko ^{[1
,2
]}

Mineharu, Yohei ^{[3
]}

Yamada, Shigeki ^{[4
]}

Nanayakkara, Shanika ^{[1
,2
]}

Matsuura, Norio ^{[1
,2
]}

Hitomi, Toshiaki ^{[1
,2
]}

Takagi, Yasushi ^{[3
]}

Hashimoto, Nobuo ^{[5
]}

Miyamoto, Susumu ^{[3
]}

Koizumi, Akio ^{[1
,2
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Hlth Sci, Kyoto 6068501, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Environm Sci, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto 6068501, Japan

[4] Shiga Med Ctr Adults, Shiga, Japan

[5] Natl Cardiovasc Ctr, Osaka, Japan

来源：

STROKE | 2010年 / 41卷 / 06期

关键词：

genetics; intracranial aneurysm; association study; CDKN2BAS; single-nucleotide polymorphisms; SUBARACHNOID HEMORRHAGE; GENOTYPING ERRORS; LINKAGE; GENETICS; LOCUS; INK4/ARF; RISK;

D O I：

10.1161/STROKEAHA.109.576694

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Purpose-Genetic factors are important determinants of intracranial aneurysm (IA). Recently, a multinational, genome-wide association study identified 3 loci associated with IA, located on 2q (rs700651), 8q (rs10958409), and 9p (rs1333040 and rs10757278). The aim of this study was to evaluate these associations. Methods-Familial and sporadic cases were investigated. Familial cases, consisting of 96 subjects with IA, and 46 subjects of unknown status from 31 pedigrees were analyzed with the transmission disequilibrium test and linkage analysis. Associations of single-nucleotide polymorphisms (SNPs) with IA were tested in 419 sporadic IA cases and in 408 control subjects. Sequencing of CDKN2A, CDKN2B, and CDKN2BAS revealed additional SNPs, and their associations with IA were also tested. Results-The transmission disequilibrium test revealed associations of 2 SNPs, rs700651 (P = 0.036) and rs1333040 (P = 0.002), with familial IA. Analysis of SNPs in sporadic cases revealed an allelic association of rs1333040 with IA (odds ratio = 1.28; 95% CI, 1.04-1.57; P = 0.02) but failed to show associations of rs10757278 and rs496892 with IA. We sequenced 3 candidate genes; CDKN2A, CDKN2B, and CDKN2BAS. All 6 index cases from IA families had the rs1333040-T allele and SNPs (rs10965215, rs10120688, and rs7341791) in CDKN2BAS. None of these SNPs had linkage disequilibrium with rs1333040 and was associated with IA. Conclusions-A region between introns 7 and 15 of CDKN2BAS carrying the rs1333040-T allele may confer risk for IA. (Stroke. 2010; 41: 1138-1144.)

引用

页码：1138 / 1144

页数：7

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