Submitted August 30, 2007
Accepted November 5, 2007
Coagulation factor XIII gene variation, oral contraceptives and risk of ischemic stroke
D. Martijn O. Pruissen, Arjen J.C. Slooter, Frits R. Rosendaal, Yolanda van der Graaf, and Ale Algra*
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands
Department of Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands
Department of Thrombosis and Hemostasis and Einthoven laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
* Corresponding author; email: a.algra{at}umcutrecht.nl.
Prothrombotic conditions are associated with ischemic stroke in young women. Particularly, the combination of oral contraceptive use and prothrombotic genetic variants appears to increase the risk of ischemic stroke. We performed a population-based case-control study in 190 women aged 20-49 years with ischemic stroke and 767 women without cardiovascular disease stratified for age, calendar year of the index event, and residence. Four variants of coagulation factor XIII subunit A and B genes (F13A1 and F13B) were investigated. The Phe allele of the F13A1 Tyr204Phe variant was present in 59 patients (31%) and 43 controls (6%); odds ratio for ischemic stroke, 9.1 for Phe/Phe and Phe/Tyr versus Tyr/Tyr genotype; 95% confidence interval, 5.5-15. Homozygous genotypes (Phe/Phe) conferred a higher risk (odds ratio 77, 95% confidence interval 7.0-848) than heterozygous (Tyr/Phe) genotypes (odds ratio 8.2, 95% confidence interval 4.9-14). The risk of ischemic stroke was further increased in carriers of the 204Phe allele using oral contraceptives (odds ratio, 20; 95% confidence interval, 9-46) as compared with nonusers with Tyr/Tyr genotype. In conclusion, the F13A1 204Phe allele was strongly associated with ischemic stroke in young women. Oral contraceptive use further increased the risk of ischemic stroke.
