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Background and Purpose  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.    Methods  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.    Results  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.    Conclusions  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.

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