Antithrombin Cambridge II(A384S) mutation frequency and antithrombin activity levels in 120 of deep venous thrombosis and 150 of cerebral infarction patients in a single center in Southern China

Zhang, Guangsen; Tang, Yang-ming; Tang, Miao; Qing, Zi-Ju; Shu, Chang; Tang, Xiangqi; Deng, Mingyang; Tan, Liming

doi:10.1097/mbc.0b013e32833dbe68

Cited by 7 publications

(9 citation statements)

References 22 publications

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“…Studies show that this mutation is associated with increased expression of thrombin. Until now, this mutation has not been identified in a Chinese population (Zhang et al, 2010).…”

Section: Antithrombin (At)mentioning

confidence: 97%

Review Common genetic risk factors of venous thromboembolism in Western and Asian populations

Huang¹,

Liu²,

Jing³

et al. 2016

Genet. Mol. Res.

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Venous thromboembolism (VTE) is a multifactorial disorder involving both acquired and genetic risk factors. The common genetic factors in Western populations have been studied and reported for several decades, while studies on Asian populations are relatively scarce. Evidence suggests that the prevalence and genetic risk factors of VTE vary significantly among ethnic populations. In this review, we summarize the common genetic risk factors of VTE in both Western and Asian populations. In addition to the development of DNA sequencing technology, genome-wide association studies have many advantages and are becoming more important in identifying new genetic risk factors and susceptible loci. They can therefore help in the prediction and prevention of VTE.

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“…Studies show that this mutation is associated with increased expression of thrombin. Until now, this mutation has not been identified in a Chinese population (Zhang et al, 2010).…”

Section: Antithrombin (At)mentioning

confidence: 97%

Review Common genetic risk factors of venous thromboembolism in Western and Asian populations

Huang¹,

Liu²,

Jing³

et al. 2016

Genet. Mol. Res.

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“…34,35 Collectively, the frequency and mutation spectrum underlying genetic thrombophilia were different among Asian countries due to the presence of population-specific prevalent mutations possibly from founder effects.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

“…2,9 Ala416Ser (or Ala384Ser) of SERPINC1 (antithrombin Cambridge II) was reported to be frequent both in VTE patients and in the general population in Britain, while it was not detected in China. 34,35 Collectively, the frequency and mutation spectrum underlying genetic thrombophilia were different among Asian countries due to the presence of population-specific prevalent mutations possibly from founder effects.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nIn this regard, we investigated the molecular genetic defects of natural anticoagulant deficiencies (PC, PS, and AT) in a large number of consecutive VTE patients and in the general population in Korea screened by coagulation tests. The results revealed unique frequencies and mutation spectrums of natural anticoagulant deficiencies in the group of VTE patients and in the general population. These frequencies and the mutation spectrums in Korea were not only distinct from those in Caucasian populations but also from those in other Asian countries. Methods Patients and populationThe group of patients consisted of consecutive VTE patients screened for thrombophilia including PC, PS, and AT deficiencies at Samsung Medical Center, Seoul, Korea, from January 2005 to December 2012. For the population group, at least 3,000 individuals visiting the institution for routine check-ups were screened from September 2005 to January 2006 using the same coagulation tests for natural anticoagulant deficiency as those used in the patients. In each group, those suspected of having a natural anticoagulant deficiency underwent molecular genetic tests to confirm the deficiency. In both groups, we excluded those with low levels of multiple (2 or more) natural anticoagulants, especially in association with underlying liver disease or other extrinsic factors. Written informed consent was obtained from the patients in the study, which was approved by the Institutional Review Board of the Samsung Medical Center, Seoul, Korea. Coagulation testsThe thrombophilia profile tests for VTE patients included screening for genetic thrombophilia: PC activity (Stachrom ® Protein C, Diagnostica Stago, Asnieres-Sur-Seine, France), PS free antigen (Liatest ® Free Protein S, Diagnostica Stago), and AT activity (Stachrom ® ATIII, Diagnostica Stago). All coagulation tests were performed on the STA ® coagulation analyzer (Diagnostica Stago). The local reference intervals were determined according to the guidelines from the Clinical and Laboratory Standards Institute (http://www.clsi.org/) as the 2.5-97.5 percentiles (PC activity, PS free antigen,.2% for males and 56.0-132.6% for females; and AT activity, 81.5-119.3%). 10 Tests for PC antigen, PS total antigen and activity, and AT antigen were additionally performed when indicated. Natural anticoagulant deficiency was suspected in VTE patients when the result was below the lower limit of the reference interval (2.5 percentile). Screening for natural anticoagulant deficiency in the population group was performed using the same coagulation tests as those used in the VTE patients. Individuals with levels of PC, PS, or AT below the 1 st percentile were selected for molecular genetic tests. Molecular genetic analysesGenomic DNA was extracted from peripheral blood leukocytes using the Wizard Genomic DNA Purification kit following the standard protocols (Promega, Madison, WI, USA). Molecular genetic diagnosis of natural anticoagulant deficiency was performed by...

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“…There are evident ethnic differences between Asians and Caucasians in the genetic features of VTE. Three prothrombotic SERPINC1 polymorphisms found in Caucasians, namely factor V Leiden, prothrombin G20210A, and antithrombin Cambridge II (p.Ala416Ser), are not found or rarely reported among Asians [ 20 , 34 , 35 ]. In contrast, two prothrombotic polymorphisms in PROC seem to be restricted to the Asian population [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Recurrent mutations in aSERPINC1hotspot associate with venous thrombosis without apparent antithrombin deficiency

Zeng

Tang

et al. 2017

Oncotarget

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Despite the essential anticoagulant function of antithrombin and the high risk of thrombosis associated with its deficiency, the prevalence of antithrombin deficiency among patients with venous thromboembolism (VTE) is very low. However, increasing evidence suggests that antithrombin deficiency may be underestimated. The analysis of SERPINC1, the gene encoding antithrombin, in 1,304 consecutive Chinese VTE patients and 1,334 healthy controls revealed a hotspot involving residues 294 and 295 that severely increases the risk of VTE. We detected the c.883G>A (p.Val295Met) (rs201381904) mutation in 11 patients and just one control (OR = 13.6; 95% CI: 1.7-107.1); c.881G>T (p.Arg294Leu) (rs587776397) in six patients but no controls; and c.880C>T (p.Arg294Cys) (rs747142328) in two patients but no controls. In addition, c.881G>A (p.Arg294His) (rs587776397) was identified in one control. These mutations were absent in a Caucasian cohort. Carriers of these mutations had normal antithrombin levels and anticoagulant activity, consistent with results obtained in a recombinant model. However, mutation carriers had a significantly increased endogenous thrombin potential. Our results suggest the existence in the Chinese population of a hotspot in SERPINC1 that significantly increases the risk of VTE by impairing the anticoagulant capacity of the hemostatic system. This effect is not revealed by current antigen or in vitro functional antithrombin assays.

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Antithrombin Cambridge II(A384S) mutation frequency and antithrombin activity levels in 120 of deep venous thrombosis and 150 of cerebral infarction patients in a single center in Southern China

Cited by 7 publications

References 22 publications

Review Common genetic risk factors of venous thromboembolism in Western and Asian populations

Review Common genetic risk factors of venous thromboembolism in Western and Asian populations

Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population

Recurrent mutations in aSERPINC1hotspot associate with venous thrombosis without apparent antithrombin deficiency

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