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Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women.

The inconsistent findings among association studies that have examined the relationship between factor XIIIA Val34Leu and thrombosis may be owing to (1) population differences in the prevalence of other risk factors that modify the association with Val34Leu, or (2) linkage disequilibrium with other functional factor XIIIA polymorphisms. We therefore performed genotyping for factor XIIIA Val34Leu, Tyr204Phe and Pro564Leu in a population-based study of myocardial infarction (MI) and ischaemic stroke among white women <45-years of age and 345 demographically similar controls, and examined potential interactions with other risk factors. The presence of the factor XIIIA Leu34 allele was associated with a slight decreased risk of MI [odds ratio (OR) = 0.80] that was most pronounced among women with traditional cardiovascular risk factors. Paradoxically, women carrying two copies of the Leu34 allele had a nearly fourfold increased risk of ischaemic stroke relative to the Val34/Val34 genotype. Heterozygosity for factor XIIIA Phe204 was associated with a milder increased risk of ischaemic stroke, and analysis of a kindred with congenital dysfibrinogenaemia suggested that co-inheritance of the factor XIIIA Phe204 allele may increase susceptibility to ischaemic stroke. Our results suggest that the factor XIIIA Val34Leu variant may be associated with a decreased risk of MI among young women with other risk factors. The relationship of factor XIIIA polymorphisms to cerebrovascular disease requires further study.

Adolescent↗

Bone healing stimulated by plasma factor XIII. Osteotomy experiments in sheep.

Sheep had their right metatarsals osteotomized midshaft and stabilized by plate and screws. One group was injected with 1250 units of Factor Thirteen for 9 days postoperatively, and a control group received placebo injections. After 8 weeks, the bones were evaluated biomechanically, histomorphologically and by densitometry. The bones of the treated group had a significantly higher tensile strength than the bones of the control animals. The correlation of biomechanical and morphological results demonstrated that the tensile strength increased with an increasing number of osteons crossing the osteotomy gap. The hydroxyapatite content of the bone healing zone was 7.3 per cent higher for the treated bones than for the control bones.

Animals↗

Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis.

It has been suggested that a G-to-T transition in exon 2 of the factor XIIIA gene resulting in a substitution of leucine for valine at amino acid 34 (FXIII Val34Leu) protects against venous thromboembolism (VTE). However, the evidence to date is insufficient to incorporate testing for the FXIII Val34Leu variant into clinical practice. To determine whether genotypes with the FXIII Val34Leu variant are protective against VTE, the authors performed a meta-analysis of 12 studies with genotyping for the FXIII Val34Leu variant (3,165 objectively diagnosed VTE cases and 4,909 controls). When a random-effects model was used, the combined odds ratios for VTE were 0.63 (95% confidence interval: 0.46, 0.86) for the homozygotes of the FXIII Val34Leu variant, 0.89 (95% confidence interval: 0.80, 0.99) for the heterozygotes, and 0.85 (95% confidence interval: 0.77, 0.95) for the homozygotes and heterozygotes combined. Potential sources of heterogeneity and potential bias were explored. The meta-analysis provided evidence that the FXIII Val34Leu variant has a small, but significant protective effect against VTE. Since VTE is a complex disorder, this information, along with results of ongoing studies to identify additional genetic factors underlying VTE, will be crucial in developing accurate risk profiles to identify individuals at higher risk of VTE.

Amino Acid Substitution↗