Association of SERPINC1 Gene Polymorphism (rs2227589) With Pulmonary Embolism Risk in a Chinese Population

Abstract

Background and Aims: Genetic variants in the gene SERPINC1 have been shown to be associated with antithrombin deficiency, which subsequently contributes to the susceptibility to venous thrombosis. However, several other studies have shown conflicting results regarding the association of SERPINC1 gene polymorphisms (rs2227589) with the risk of thrombosis. Hence, in the present study, we conducted a case-control study to further evaluate the association between the variant rs2227589 with antithrombin deficiency in pulmonary embolism (PTE). A pooled systematic analysis was also conducted to evaluate the risk of rs2227589 in venous thromboembolism (VTE) among multiple populations.Methods: This case-control study involved 101 patients and 199 healthy controls. The allele frequency of SERPINC1 variant rs2227589 was analyzed by Sequenom assay. Antithrombin anticoagulant activity was detected using an automatic coagulation analyzer. In addition, a pooled systematic analysis on 10 cohorts consisting of 5,518 patients with VTE and 8,935 controls was performed.Results: In total, 27 (26.7%) PTE subjects were diagnosed as having antithrombin deficiency. Our results showed that antithrombin plasma activity was slightly lower in T allele carriers than that in C allele carriers. However, there was no significant correlation between rs2227589 genotype and antithrombin anticoagulant activity. The recessive model showed that rs2227589 was significantly associated (p = 0.026) with an increased risk {odds ratio [OR]: 2.31, 95% confidence interval [CI] (1.09–4.89)} of Chinese PTE. The pooled systematic analysis of all case-control study and meta-analysis showed that rs2227589 polymorphism was associated with an increased risk of VTE in the additive model [OR: 1.09, 95% CI (1.01–1.18), P = 0.029] and dominant model [OR: 1.10, 95% CI (1.01–1.20), P = 0.034].Conclusions: Our study demonstrated that variant rs2227589 is associated with an increased risk of PTE in a Chinese population but no correlation with antithrombin anticoagulant activity. However, pooled systematic analysis of multiple populations showed a significant association between rs2227589 and the risk of VTE in the additive and dominant genetic model.

Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis

“…Several limitations should be discussed in this study. First, antithrombin activity was not measured and the SERCPINC1 gene was not sequenced, although they are major etiological factors in other Asian populations 13,26,33 . Second, gross deletions/duplications in PROS1 were found to be relatively common in hereditary protein S‐deficient patients who were negative for point mutation 34 ; however, multiplex ligation‐dependent probe amplification was not performed.…”

Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes

“…Surgery, trauma, sedentary, pregnancy, and cancer are considered acquired risk factors of VTE. Studies have demonstrated that genetic factors are responsible for more than 60% of common thrombotic susceptibility ( Yue et al, 2019 ).…”