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Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

ABSTRACT: BACKGROUND: ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population. METHODS: We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction. RESULTS: The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0. INTERPRETATION: ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

SUBMITTER: Sode BF

PROVIDER: S-EPMC3602271 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

Sode Birgitte F BF Allin Kristine H KH Dahl Morten M Gyntelberg Finn F Nordestgaard Børge G BG

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20130204 5

<h4>Background</h4>ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.<h4>Methods</h4>We used data from 2 Danish studies that followed members of the general publi ...[more]

PMID: 23382263

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Project description:Abstract Introduction Venous thromboembolic events (VTE) are common complications in patients with glioblastoma (GBM). Factor V Leiden (FVL) polymorphism (rs6025, c.1601 G>A) is a known risk factor for VTE, evaluated in cancer associated thrombosis (CAT) in different tumor types. Little is known about the role of this variant in development of CAT in patients with GBM. Material and Methods A cohort of 116 GBM patients (73 males and 43 females) all treated with concomitant temozolomide and radiotherapy, were genotyped for FVL using PCR- pyrosequencing. Of the cohort, 40 patients were diagnosed with and 76 without VTE. Allele frequencies of respective variant were also compared with data from the SweGen Variant Frequency Browser (https://swegen-exac.nbis.se/). Statistical analyses in regard to VTE and its association with FVL and prognostic factors were performed. Results The variant A/G of FVL was carried by 17 (15%) of the patients and 99 (85%) were wild type, G/G. Chi2 test including the prognostic factors age, type of surgery, gender and blood group showed that these were evenly distributed between those with G/G and A/G, except for blood group in relation to FVL variant, which showed a borderline significance (p=0.07). Among the patients having blood group 0, 32% (n= 32) were G/G and 59% (n= 10) were A/G. Statistical tests did not reveal any correlation between blood group and FVL variant. In the logistic regression analysis apart from FVL, age, gender and blood group were included. This showed a significant difference for blood group 0 versus non-0 (A, B or AB) for decreased risk of VTE (P=0.014). There was no significant difference between heterozygous FVL (A/G) versus the G/G genotype in VTE risk (p=0.09). There were no differences in survival in relation to VTE or not or variant of FVL. The FVL AG variant is slightly overrepresented among GBM compared to the normal Swedish population, but does not reach statistical significance, OR 1.63 (0.93–2.84). Conclusions We examined the influence of FVL variants together with clinical factors in a homogenously treated cohort of GBM patients for the risk to develop a VTE. We confirmed blood group 0 versus non-0 as reducing the VTE risk. For FVL c.1601 G>A variant, the differences between AG vs GG did not reach statistical significance. In our cohort we found a trend towards increased risk of developing GBM for the A/G variant. We plan to further study other factors involved in coagulation for their potential role in GBM patients.

Dataset Information

Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

Publications

Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

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