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Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age

Journal article
Authors Ellen Hanson
Staffan Nilsson
Katarina Jood
Bo Norrving
Gunnar Engström
Christian Blomstrand
Arne Lindgren
Olle Melander
Christina Jern
Published in PLoS ONE
Volume 8
Issue 9
Pages artikel nr e75286
ISSN 1932-6203
Publication year 2013
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Department of Mathematical Sciences, Mathematical Statistics
Pages artikel nr e75286
Language en
Links dx.doi.org/10.1371/journal.pone.007...
https://gup.ub.gu.se/file/111763
Keywords Haplotypes, Hemorrhage, Blood plasma, Genotyping, Genetics of disease, Diet, Thrombin, Ischemic stroke
Subject categories Clinical Medicine

Abstract

Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmö Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample ≤70 years. We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.

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