Gene Variants Associated With Venous Thrombosis: A Replication Study in a Brazilian Multicentre Study

Abstract

Single nucleotide polymorphisms (SNP) associated with Venous Thromboembolism (VTE) risk have been identified in European and American populations. Replicate SNPs associated with VTE in a Brazilian multicenter case-control study of the Southeast region. Patients with previous VTE assisted at the Outpatient Clinics of 3 centers of the Southeast Brazilian region were compared to normal controls of the same geographic region. We evaluated 29 SNPs associated with VTE risk in other populations, and 90 SNPs for stratification analysis of the population. Due to high admixture of Brazilian population and lack of previous studies, the calculation of the sample power was performed after genotyping. Sample size, allelic frequency and Hardy-Weinberg equilibrium were estimated. The association and odds ratio analyses were estimated by logistic regression and the results were adjusted for multiple tests using Bonferroni correction. The evaluation of the genetic structure similarity in the cases and controls was performed by AMOVA. 436 cases and 430 controls were included. It was demonstrated that this sample has a statistical power to detect a genetic association of 79.4%. AMOVA showed that the genetic variability between groups was 0.0% and 100% within each group. None of the SNPs showed association with VTE in our population. A Brazilian multicenter case-control study with adequate sample power, high genetic variability though no stratification between groups, showed no replication of SNPs associated with VTE. The high admixture of Brazilian population may be responsible for these results, emphasizing the influence of the population genetic structure in association studies.

Genetic Predisposition of Both Waist Circumference and Hip Circumference Increased the Risk of Venous Thromboembolism

“…32 Some thrombogenic genes have been confirmed to have common loci and low-frequency susceptibility alleles. 30 The introduction of GWAS enabled the identification of genetic alterations associated with complex diseases. 30 Ahmad et al held the honor that a single gene biomarker could not accurately predict the risk of VTE recurrence, 33 or develop a multiple SNP model to predict the risk of VTE recurrence.…”

“…30 The introduction of GWAS enabled the identification of genetic alterations associated with complex diseases. 30 Ahmad et al held the honor that a single gene biomarker could not accurately predict the risk of VTE recurrence, 33 or develop a multiple SNP model to predict the risk of VTE recurrence. 33 In fact, no single genetic defect can predict the risk of VTE recurrence.…”

“… 29 The most prominent genetic risk factors for VTE are deficiencies of the natural anticoagulants (antithrombin, protein C, and protein S) and genetic mutations associated with coagulation factors such as factor V Leiden (FVL), factor II, and factor XI (FXI) mutations. 3 30 31 However, the main hereditary thrombotic disorders such as antithrombin, protein C, and protein S deficiency accounted for only 5 to 10% of cases. 32 Some thrombogenic genes have been confirmed to have common loci and low-frequency susceptibility alleles.…”

“…However, the main hereditary thrombotic disorders such as antithrombin, protein C, and protein S deficiency, accounted for only 5-10 % of cases [32] . Some thrombogenic genes have been confirmed to have common loci and low-frequency susceptibility alleles [30] . The introduction of GWAS enabled the identification of genetic alterations associated with complex diseases [30] .…”

“…At least one genetic risk factor can be identified in about half of cases of first-episode idiopathic VTE [29] . The most prominent genetic risk factors for VTE are deficiencies of the natural anticoagulants (antithrombin, protein C, and protein S) and genetic mutations associated with coagulation factors such as Factor V Leiden (FVL), Factor II and Factor XI (FXI) mutations [3,30,31] . However, the main hereditary thrombotic disorders such as antithrombin, protein C, and protein S deficiency, accounted for only 5-10 % of cases [32] .…”