No association between thrombosis and factor V gene polymorphisms in Chinese Han population

SummaryActivated protein C resistance (APCR) is the most common hereditary condition of thrombosis in Western countries. And it is significantly linked to a single nucleotide polymorphisms (SNPs) in the coagulation factor V gene that results in the mutations at R506, R306 and HR2 alleles. To determine the prevalence of APCR and its association with the factor V gene SNPs in Chinese Han thrombotic patients, we investigated a total of 346 Chinese thrombotic patients and 140 normal controls for APCR using the APTT-based assays, according to manufacturer’s instructions, APC ratio ≦2 indicated APC resistance. Mutations of factor V at R506, R306, HR2 allele were detected by PCRMnl/I, Bst/NI, Rsa/I digestion as described before respectively. The results showed that the incidence of APC resistance were 12.0% (12 of 100 cases) in acute cerebral thrombosis (ACT) patients (P <0.05), 13.5% (13 of 96 cases) in acute myocardial infarction (AMI) patients (P <0.05), 16.7% (10 of 60 cases) in deep venous thrombosis (DVT) patients (P <0.05), 15.6% (14 of 90 cases) in systemic lupus erythematosus (SLE) patients (P <0.05) and 5.0% (7 of 140 cases) in normal controls. APCR is associated with thrombotic events. But no factor V R506Q mutation (FV Leiden) was found in all 5 groups. Only one AMI patient and one DVT patient revealed heterozygous R306G mutation, which was confirmed by direct sequencing PCR products. Additionally, two SLE patients showed to be heterozygous HR2 allele for the first time in the Chinese Han population. We concluded that APC resistance in the Chinese Han population might not be associated with mutations of factor V at R506, R306 and HR2 polymorphisms. Some other factors might contribute to APC resistance in the Chinese Han population.

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Coagulation factor V gene 1691G>A polymorphism as an indicator for risk and prognosis of lower extremity deep venous thrombosis in Chinese Han population

Medicine ◽

10.1097/md.0000000000010885 ◽

2018 ◽

Vol 97 (22) ◽

pp. e10885

Author(s):

Chang-Lie Zhang ◽

Zun-Min Li ◽

Zhi-Hong Song ◽

Tao Song

Keyword(s):

Lower Extremity ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Coagulation Factor ◽

Factor V ◽

Chinese Han ◽

Han Population ◽

Coagulation Factor V ◽

Factor V Gene ◽

V Gene

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Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene

Thrombosis Research ◽

10.1016/0049-3848(95)00048-v ◽

1995 ◽

Vol 78 (3) ◽

pp. 193-200 ◽

Cited By ~ 33

Author(s):

Maria I. Bokarewa ◽

Katarina Bremme ◽

Gunnar Falk ◽

Margareta Sten-Linder ◽

Nils Egberg ◽

...

Keyword(s):

Coagulation Factor ◽

Factor V ◽

Apc Resistance ◽

Coagulation Factor V ◽

Factor V Gene ◽

V Gene

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New Coagulation Factor V Gene Polymorphisms Define a Single and Infrequent Haplotype Underlying the Factor V Leiden Mutation in Mediterranean Populations and Indians

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657683 ◽

1997 ◽

Vol 78 (03) ◽

pp. 1037-1041 ◽

Cited By ~ 16

Author(s):

E Castoldi ◽

B Lunghi ◽

F Mingozzi ◽

P Loannou ◽

G Marchetti ◽

...

Keyword(s):

Direct Sequencing ◽

Factor V Leiden ◽

Coagulation Factor ◽

Specific Factor ◽

Mutational Event ◽

Factor V ◽

Factor V Leiden Mutation ◽

Mediterranean Populations ◽

Factor V Gene ◽

V Gene

SummaryTwo novel polymorphisms were identified in the factor V gene by direct sequencing of intronic areas. One of them, located in intron 9, is the marker closest to the Leiden mutation ever described, whereas the other, in intron 16, displays a rare allele invariantly associated to the mutation. Allele-specific amplification protocols were designed to perform extensive screenings for both polymorphic sites. The new markers were used in combination with six previously described polymorphisms to define specific factor V gene haplotypes. Haplotype investigations in 506Q homozygous thrombotic patients and normal controls showed the presence of a single haplotype underlying the factor V Leiden mutation in Mediterranean populations (among which Greek Cypriots, where the R506Q mutation is particularly frequent) and Indians. When traced in the absence of the Leiden mutation, the background haplotype was found to be present and roughly as frequent as the mutation itself in these populations. These findings indicate a single mutational event, that probably occurred outside Europe, as the cause of the Leiden mutation and provide a powerful tool to investigate its evolutionary history.

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Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650259 ◽

1996 ◽

Vol 75 (02) ◽

pp. 270-274 ◽

Cited By ~ 57

Author(s):

Benget Zöller ◽

Johan Holm ◽

Peter Svensson ◽

Björn Dahlbäck

Keyword(s):

Plasma Concentration ◽

Protein C ◽

Protein S ◽

Factor V ◽

Protein S Deficiency ◽

Apc Resistance ◽

S Deficiency ◽

Increased Risk ◽

Factor V Gene ◽

V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

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Factor V Kuwait: A Novel Mutation in the Coagulation Factor V Gene Discovered in Kuwait

Medical Principles and Practice ◽

10.1159/000090912 ◽

2006 ◽

Vol 15 (2) ◽

pp. 102-105

Author(s):

Mehrez M. Jadaon ◽

Ali A. Dashti ◽

Hend L. Lewis

Keyword(s):

Novel Mutation ◽

Coagulation Factor ◽

Factor V ◽

Coagulation Factor V ◽

Factor V Gene ◽

V Gene

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A Factor V Genetic Component Differing From Factor V R506Q Contributes to the Activated Protein C Resistance Phenotype

Blood ◽

10.1182/blood.v90.4.1552 ◽

1997 ◽

Vol 90 (4) ◽

pp. 1552-1557 ◽

Cited By ~ 127

Author(s):

F. Bernardi ◽

E.M. Faioni ◽

E. Castoldi ◽

B. Lunghi ◽

G. Castaman ◽

...

Keyword(s):

Venous Thromboembolism ◽

Protein C ◽

Activated Protein C ◽

Functional Assay ◽

Factor V ◽

Resistance Phenotype ◽

Apc Resistance ◽

Genetic Components ◽

Factor V Gene ◽

V Gene

AbstractFactor V gene polymorphisms were investigated to detect components that may contribute to the activated protein C (APC) resistance phenotype in patients with venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by six polymorphisms and its frequency was found to be similar in normal subjects coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was originated by ancestral mutational events. The relationship between the distribution of normalized APC ratios obtained with the functional assay and haplotype frequency was analyzed in patients heterozygous for factor V R506Q (factor V Leiden). The HR2 haplotype was significantly more frequent in patients with ratios below the 15th percentile than in those with higher ratios or in normal controls. Moreover, the study of 10 patients with APC resistance in the absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2 homozygotes. The HR2 haplotype was associated with significantly lower APC ratios both in patients with venous thromboembolism and in age- and sex-matched controls. However, the two groups showed similar HR2 haplotype frequencies. Plasma mixing experiments showed that an artificially created double heterozygote for the factor V R506Q mutation and the HR2 haplotype had an APC ratio lower than that expected for a simple R506Q heterozygote. Time-course experiments evaluating the decay of factor V in plasma showed the normal stability of the molecule encoded by the factor V gene marked by the HR2 haplotype, which ruled out the presence of a pseudo-homozygous APC resistance mechanism. Our results provide new insights into the presence of factor V genetic components other than the factor V R506Q that are able to contribute to the APC resistance phenotype in patients with venous thromboembolism.

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Expression of coagulation factor V gene by normal adult human hepatocytes in primary culture

British Journal of Haematology ◽

10.1111/j.1365-2141.1991.tb04421.x ◽

1991 ◽

Vol 78 (2) ◽

pp. 229-235 ◽

Cited By ~ 9

Author(s):

Marlene Mazzorana ◽

Georges Baffet ◽

Bernard Kneip ◽

Bernard Launois ◽

Christiane Guguen-Guillouzo

Keyword(s):

Primary Culture ◽

Coagulation Factor ◽

Human Hepatocytes ◽

Normal Adult ◽

Factor V ◽

Adult Human ◽

Coagulation Factor V ◽

Factor V Gene ◽

V Gene

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Correlation between miRNA target site polymorphisms in the 3′ UTR of AVPR1A and the risk of hypertension in the Chinese Han population

Bioscience Reports ◽

10.1042/bsr20182232 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 1

Author(s):

Liuping Zhang ◽

Jinwei Liu ◽

Peng Cheng ◽

Fangchao Lv

Keyword(s):

Single Nucleotide Polymorphisms ◽

Mirna Target ◽

Direct Sequencing ◽

Chinese Han Population ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Increased Risk

Abstract We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3′ UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231–1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092–1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

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