Frequency of thrombophilia associated genes variants: population-based study

Abstract Background Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations. Methods All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay. Results The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G > A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects. Conclusion The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).

Download Full-text

Frequency of thrombophilia associated genes. Population – based study.

10.21203/rs.2.13327/v2 ◽

2020 ◽

Author(s):

Natalia Wawrusiewicz-Kurylonek ◽

Adam Jacek Kretowski ◽

Renata Posmyk

Keyword(s):

Coagulation Factor ◽

Population Based ◽

Taqman Assay ◽

Factor V ◽

Population Based Study ◽

Inherited Thrombophilia ◽

Pathogenic Variants ◽

South Central ◽

Coagulation Factor V ◽

Main Factor

Abstract Background: Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor ( FV ) and the prothrombin ( FII ) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations. Methods: All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay. Results: The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G>A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects. Conclusions: The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).

Download Full-text

Frequency of thrombophilia associated genes. Population – based study.

10.21203/rs.2.13327/v3 ◽

2020 ◽

Author(s):

Natalia Wawrusiewicz-Kurylonek ◽

Adam Jacek Kretowski ◽

Renata Posmyk

Keyword(s):

Coagulation Factor ◽

Population Based ◽

Taqman Assay ◽

Factor V ◽

Population Based Study ◽

Inherited Thrombophilia ◽

Pathogenic Variants ◽

South Central ◽

Coagulation Factor V ◽

Main Factor

Abstract Background: Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations. Methods: All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay. Results: The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G>A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects. Conclusion: The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).

Download Full-text

Frequency of trombophilia associated genes. Population – based study.

10.21203/rs.2.13327/v1 ◽

2019 ◽

Author(s):

Natalia Wawrusiewicz-Kurylonek ◽

Adam Jacek Kretowski ◽

Renata Posmyk

Keyword(s):

Coagulation Factor ◽

Population Based ◽

Taqman Assay ◽

Factor V ◽

Eastern European ◽

Population Based Study ◽

Inherited Thrombophilia ◽

Pathogenic Variants ◽

Coagulation Factor V ◽

Eastern European Countries

Abstract Background: Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor that promotes venous (rarely arterial) thromboembolism (VTE). The inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as an inherited thrombophilia factor in a representative group of Polish population in comparison with other described populations. Methods: All studied groups consisted of 1414 unrelated patients at the age between 18 and 70. The individuals from the research group came from the Podlasie region of Poland. Genotyping of FII, FV and MTHFR variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay. Results: The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G>A variant) were observed only in 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-instability of heterozygous genotype GA of variants FII and FV genes was observed only in 4 subjects. Conclusions: Our results is similar to the frequency of the both FII and FV variants in the South–Eastern European countries population, whose value is about 5% and 2.5% respectively.

Download Full-text

Prevalence of Variants in Candidate Genes for Type 2 Diabetes Mellitus in The Netherlands: The Rotterdam Study and the Hoorn Study1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.3.5563 ◽

1999 ◽

Vol 84 (3) ◽

pp. 1002-1006

Author(s):

Leen M. 't Hart ◽

Ronald P. Stolk ◽

Jacqueline M. Dekker ◽

Giel Nijpels ◽

Diederick E. Grobbee ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Receptor ◽

Coagulation Factor ◽

Population Based ◽

Factor V ◽

Rotterdam Study ◽

Coagulation Factor V

We have analyzed the association of variants in the genes for amylin, insulin receptor, insulin receptor substrate-1 (IRS-1), and coagulation factor V with type 2 diabetes mellitus. Random samples of subjects with type 2 diabetes and controls were taken from two population-based studies, the Hoorn and Rotterdam studies, to reduce the risk of artifactual associations. No association was found for variants in the genes for amylin, IRS-1, and coagulation factor V, nor was there any evidence for epi-static interactions between these gene variants. A significant difference in the frequency of the Arg972 allele of the IRS-1 gene was observed between control subjects from Hoorn and Rotterdam (9.4% vs. 18.6%; P < 0.05). The insulin receptor Met985 variant was found at frequencies of 4.4% and 1.8%, respectively, in type 2 diabetic (n = 433) and normoglycemic patients (n = 799; P < 0.02). Inclusion of data from two other studies yielded a summarized odds ratio of 1.87 (95% confidence interval, 1.06–3.29; P = 0.03). We conclude that the association between the Met985 variant in the insulin receptor gene and type 2 diabetes, which we previously reported in the Rotterdam study, is supported by the joint analysis with a second population-based study and other studies. The large regional differences in allele frequency of the Arg972 allele of IRS-1 gene makes genetic association studies of this gene less reliable.

Download Full-text

Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615201 ◽

1998 ◽

Vol 80 (08) ◽

pp. 344-345 ◽

Cited By ~ 2

Author(s):

Pasra Arnutti ◽

Motofumi Hiyoshi ◽

Wichai Prayoonwiwat ◽

Oytip Nathalang ◽

Chamaiporn Suwanasophon ◽

...

Keyword(s):

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Coagulation Factor ◽

Factor V ◽

Activated Protein C Resistance ◽

Factor V Leiden Mutation ◽

Coagulation Factor V

Download Full-text

Phenotyping and Genotyping of Coagulation Factor V Leiden

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650258 ◽

1996 ◽

Vol 75 (02) ◽

pp. 267-269 ◽

Cited By ~ 27

Author(s):

H Engel ◽

L Zwang ◽

H H D M van Vliet ◽

J J Michiles ◽

J Stibbe ◽

...

Keyword(s):

Factor V Leiden ◽

Coagulation Factor ◽

Diagnostic Value ◽

Resistance Test ◽

Amplification Refractory Mutation System ◽

Factor V ◽

Chain Reactions ◽

Apc Resistance ◽

Specificity And Sensitivity ◽

Coagulation Factor V

SummaryThe currently used activated Protein C resistance test demonstrated to be of limited diagnostic value for the detection of the mutant Factor V Leiden. Moreover, this assay is not useful for patients under anticoagulant therapy. A modification of the APC resistance test, applying Factor V deficient plasma is described which demonstrates a specificity and sensitivity of 1.0. The superiority of the modified APC resistance test over the existing APC resistance test was verified by genotyping.For that purpose, the Amplification Refractory Mutation System (ARMS) was applied to the detection of the G to A mutation at position 1691 in the gene encoding coagulation Factor V. The mutation at that position could be easily detected by using each of two allele-specific oligonucleotide primers concomitantly with one common primer in two separate polymerase chain reactions, thereby amplifying a fragment of 186 base-pairs of the Factor V gene.

Download Full-text