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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Association of kallikrein gene polymorphisms with intracranial aneurysms
Stroke, Volume 38, No. 10, Year 2007
Notification
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Description
BACKGROUND AND PURPOSE - Genomewide DNA linkage analysis identified a susceptibility locus for intracranial aneurysm (IA) on chromosome 19q13 in the Finnish population, a region including the kallikrein gene cluster. We investigated the association of single nucleotide polymorphisms (SNPs) in the kallikrein gene cluster with IA in the Finnish population. METHODS - We genotyped 18 haplotype-tagging SNPs spanning a 244 kbp region in the kallikrein gene cluster for 266 Finnish IA cases and 290 Finnish control subjects. In a second phase, we genotyped 2 SNPs (rs1722561 and rs1701946) in an additional set of 102 Finnish IA cases and 102 Finnish control subjects; and in a third phase, we genotyped these 2 SNPs in 156 Russian IA cases and 186 Russian control subjects. Both single-marker and haplotype-based tests of association were performed. RESULTS - In phase I, SNPs rs1722561 and rs1701946 were significantly associated with IA in the Finnish population for single locus models (rs1722561: P=0.0395; rs1701946: P=0.0253). A 2-SNP haplotype block (rs1722561-rs1701946) identified in phase I was also associated with IA in the expanded Finnish (phase II) data set (asymptotic P=0.012; empirical P=0.019). In the Finnish and Russian combined data set (phase III) with 524 cases and 578 control subjects, the same 2 SNPs (OR: 1.35, 95% CI: 1.14, 1.60; P=0.0005 for rs1722561 and OR: 1.32, 95% CI: 1.12, 1.57; P=0.0011 for rs1701946) were significantly associated with IA. These SNPs are located in the intronic region of KLK8, although linkage disequilibrium could extend from rs268912-rs2250066, a ≈76-kbp region that includes KLK5-KLK10. CONCLUSIONS - Polymorphisms within the kallikrein gene cluster are associated with IA suggesting that the kallikreins are important candidate genes for IA. © 2007 American Heart Association, Inc.
Authors & Co-Authors
Goddard, Katrina A.B.
United States, Cleveland
Case Western Reserve University
Parrado, Antonio R.
United States, Cleveland
Case Western Reserve University
Lebedeva, Elena R.
Russian Federation, Yekaterinburg
Ural State Medical University
Ronkainen, Antti
Finland, Kuopio
Kuopio University Hospital
Niemelä, Mika R.
Finland, Helsinki
Helsinki University Hospital
Khusnutdinova, Ehl'za Kh
Russian Federation, Moscow
Russian Academy of Sciences
Khusainova, Rita I.
Russian Federation, Moscow
Russian Academy of Sciences
Jääskeläinen, Juha Erik
Finland, Kuopio
Kuopio University Hospital
Kuivaniemi, Helena
United States, Detroit
Wayne State University
Tromp, Gerard C.
United States, Detroit
Wayne State University
United States, Detroit
Wayne State University School of Medicine
Statistics
Citations: 31
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1161/STROKEAHA.107.486225
ISSN:
00392499
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study