Impact of genetic polymorphisms in thrombin activatable fibrinolysis inhibitor (TAFI) on venous thrombosis disease: A meta-analysis

Qian, Kai; Xu, Jie; Wan, Heng; Fu, Fang-yong; Lu, Jing-Bo; Lin, Zhiqi; Liu, Zhengjun; Líu, Hao

doi:10.1016/j.gene.2015.06.014

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…We showed that when the Ala147Thr variant is analyzed in males and females combined, there is no observed association with thrombotic events (OR = 0.94, p = 0.128). These results are consistent with previous results of a meta-analysis of this variant with coronary heart disease [34] but inconsistent with a recent meta-analysis with venous thrombosis [56], which reported an association across all genetic models.…”

Section: Discussionsupporting

confidence: 71%

“…Despite the critical hemostatic role of TAFI, epidemiological studies on the effect of the above common TAFI-associated variants on the risk venous thrombosis are inconclusive [32, 34–55] with inconsistent results between studies, and a recent meta-analysis [56] that has important methodological limitations. We speculate that these inconsistencies could be due to the interaction of these variants with sex on the risk of thrombotic events, and to the lack of statistical power of individual studies.…”

Section: Introductionmentioning

confidence: 99%

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Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

et al. 2017

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BackgroundThrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis.MethodsA comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models.ResultsA total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96–1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71–0.97, p = 0.021) for venous thrombosis.ConclusionsA comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

et al. 2017

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“…15 These findings were consistent for patients with CVT, with no significant association for thrombosis risk. 23…”

Section: Discussionmentioning

confidence: 99%

Thrombin-Activatable Fibrinolysis Inhibitor Polymorphisms and Cerebral Venous Thrombosis in Mexican Mestizo Patients

Araúz

Argüelles

Jara

et al. 2018

Clin Appl Thromb Hemost

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Thrombin-activatable fibrinolysis inhibitor (TAFI) gene polymorphisms have been proposed as a predisposing factor for cerebral venous thrombosis (CVT). We analyzed the association between CVT and TAFI single-nucleotide polymorphisms (rs3742264, rs2146881, and rs1926447) compared to healthy controls. Mexico Mestizo confirmed cases with CVT and age- and sex-matched controls with no history of venous thrombotic events were recruited from July 2006 to July 2015. Demographic, clinical, and imaging information was included in the analysis. Genotyping single-nucleotide polymorphisms were performed by allele-specific polymerase chain reaction. Allelic univariate analysis, haplotype association, and Hardy-Weinberg equilibrium were assessed. A total of 113 CVT cases (94 females [83.2%]; median age 35 years [interquartile range 27-43 years]) and 134 age- and sex-matched controls were included. The main risk factors for CVT were pregnancy/puerperium (30.9%), oral contraceptive use (19.5%), and hereditary thrombophilia (7.1%). We found no significant association for heterozygous and homozygous models for rs3742264 ( P = .30 and P = .69, respectively), rs2146881 ( P = .90 and P = .17, respectively), or rs1926447 ( P = .40 and P = .52, respectively) compared to controls; these findings were consistent in subgroup and haplotype analyses. In conclusion, TAFI rs3742264, rs2146881, and rs1926447 polymorphisms do not increase the risk of CVT in comparison to healthy controls.

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“…However, there is still no definite evidence concerning the association between TAFI polymorphisms and venous thrombosis risk. Our previous metaanalysis performed in the same way investigated the association between the three TAFI polymorphisms and venous thrombosis risk [32]. However, some defects existed in the literature included; an article that did not report a venous thrombosis case-control study and mainly researched pediatric oncology patients [33] was falsely included.…”

Section: Discussionmentioning

confidence: 99%

Association between thrombin-activatable fibrinolysis inhibitor gene polymorphisms and venous thrombosis risk

Wang

Ma²,

Lü³

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

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Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important antifibrinolytic factor that has been shown in increased concentrations to be associated with an increased risk for venous thrombosis. However, the effect of TAFI gene polymorphisms on the risk of venous thrombosis remains debatable. The aim of the current study was to evaluate the association of three single nucleotide polymorphisms: 505G>A (rs3742264), 1040 C>T (rs1926447) and -438G>A (rs2146881) with venous thrombosis risk using a meta-analysis. A systematic literature search for eligible studies published before 20 January 2015 was conducted in PubMed, EMBASE, Web of Science, WanFang database and Chinese National Knowledge Infrastructure. We assessed the possible association by pooled odds ratio and its 95% confidence interval. A total of 14 independent case-control studies including 2970 cases and 3049 controls were enrolled in the final meta-analysis. A significant reduction of venous thrombosis risk in the 505G>A polymorphism was observed under allele comparison, homozygote comparison and recessive models, but opposite results were seen in Asians. Likewise, there was a significant decreased susceptibility to venous thrombosis in the 1040C>T polymorphism in homozygote comparison and recessive models. In the subgroup analysis, the nonvenous thromboembolism disease group showed a significantly increased venous thrombosis risk. Pooled estimates did not show evidence of association between -438G>A and venous thrombosis risk in any genetic model. This meta-analysis suggested that although the -438G>T polymorphism is not correlated with venous thrombosis risk in all models, a trend toward reduced risk still could be observed. The A allele and AA genotype of 505G>A in whites and the TT genotype of 1040C>T were significantly associated with a decreased risk of venous thrombosis, except in the non-venous thromboembolism group.

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Impact of genetic polymorphisms in thrombin activatable fibrinolysis inhibitor (TAFI) on venous thrombosis disease: A meta-analysis

Cited by 9 publications

References 38 publications

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

Thrombin-Activatable Fibrinolysis Inhibitor Polymorphisms and Cerebral Venous Thrombosis in Mexican Mestizo Patients

Association between thrombin-activatable fibrinolysis inhibitor gene polymorphisms and venous thrombosis risk

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