MedWire News: Variant forms of the gene encoding factor (F)XI (F11) are associated with an increased risk for deep vein thrombosis (DVT), shows research published in the Journal of Thormbosis and Haemostasis.
The investigators found that F11 SNPs were also associated with elevated FXI, a known thrombophilic factor, but that the link between the SNPs and DVT risk continued even after adjusting for FXI levels.
“One possible explanation is that these SNPs may more accurately assess average intra-individual FXI levels than a single FXI level measurement. That is, day to day variation in FXI levels could result in an aberrant result for a single FXI level determination while the genotype of a SNP associated with FXI levels does not change,” hypothesize Frits Rosendaal (Leiden University Medical Center, The Netherlands) and co-workers.
Alternatively, the SNPs may alter FXI expression in response to age or hormone levels or affect expression of other DVT-associated proteins, they suggest.
Previously, research has linked the risk for DVT with single nucleotide polymorphisms (SNPs) detected in the 4q35.2 locus, which contains F11, the cytochrome P450 family member CYP4V2 and prekallikrein (KLKB1).
To investigate further, the team examined 103 SNPs present in this region among participants of the Leiden Thrombophilia Study (443 DVT patients and 453 controls) and the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study (2712 DVT patients and 4634 controls).
Analysis showed that carriage of the F11 SNPs rs2289252 and rs2036914 significantly increased the risk for DVT, with odds ratios of 1.49 and 1.33, respectively, after adjusting for age, gender, and the other F11 SNP.
Noting that rs2036914 has been previously linked to FXI levels, the team investigated the association between FXI and rs2289252, finding that carriers of the TT genotype had significantly higher levels than those with the CC or CT genotype.
Commenting on the current study, the researchers note that other single nucleotide polymorphisms (SNPs) in the region may also alter DVT risk but that the study was underpowered to detect them, and was unable to identify other variants, such as insertion or deletion mutations.
Future technologies and functional studies may be required to detect further variants associated with DVT in this region, they conclude.
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