Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians

Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among healthy young adults, since only few cases were found to be carriers for the two alleles.     

Prevalence of coagulation factor II G20210A and factor V G1691A Leiden polymorphisms in Chechans, a genetically isolated population in Jordan

Background Coagulation factor II G20210A and coagulation factor V (Leiden) G1691A single nucleotide polymorphisms (SNPs) are major inherited risk factors of venous thromboembolism. In view of the heterogeneity in their world distribution and lack of sufficient information about their distribution among Chechans, we addressed the prevalence of these SNPs in the Chechan population in Jordan, a genetically isolated population. Methods and Results factor II G20210A and factor V Leiden SNPs were analysed by polymerase chain reaction and restriction fragment length polymorphism (PCR?CRFLP) method and Amplification refractory mutation detection system (ARMS) respectively in 120 random unrelated subjects from the Chechan population in Jordan. Among the subjects studied for factor II G20210A mutation there were three individuals carrying this mutation as heterozygous (one female and two male), giving a prevalence of 2.5?% and an allele frequency of 1.25?%. No homozygous factor II allele was found. Factor V Leiden G1691A mutation was detected as heterozygous in 22 of 120 of individuals (17 female and five male) indicating a prevalence of 18.3?% and allele frequency of 9.2?%. No homozygous allele was found. Conclusion Our results indicated that prevalence of factor II G20210A mutation in the Chechan population is similar to prevalence in Jordan and Caucasian populations (1?C6?%) while the prevalence of factor V Leiden was higher in the Chechan population compared to Jordan and Caucasian populations (2?C15?%).     

Multiplex PCR-RFLP assay for detection of factor V Leiden and prothrombin G20210A

Factor V Leiden and prothrombin G20210A are clinically relevant genetic risk factors for venous thrombosis. Molecular diagnostic testing for factor V Leiden and prothrombin G20210A is widespread, and laboratories use a variety of technical approaches. Here we introduce a multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based on single (Mn/l) restriction endonuclease digestion. The assay was shown to simultaneously and accurately detect factor V Leiden and prothrombin G20210A mutations.     

Thrombophilic gene polymorphism studies in G6PD deficient individuals from Saudi population

We performed a study to evaluate the role of three single nucleotide polymorphisms (SNPs), factor V Leiden G1691A (FVL), prothrombin gene mutation G20210A (PRT or FII-G20210A) and methylenotetrahydrofolate reductase variant C677T (MTHFRC677T), as risk factors for G6PD in Saudi populations. Our results did not show any association with the three Thrombophilic genes with FVL gene, no statistical analysis have shown any association with either allele or genotype frequencies OR=0.566, p=.0.667, (95% CI=0.014-22.48) and OR=0.569, p=0.251¸ (95% CI=0.014-22.96).In PRT gene G20210A for G Vs A, p=0.774; OR=0.566 (95%CI; 0.011-29.6); AA+GA Vs GG; p=0.502; OR=0.569 (95%CI=0.010-2969). G and A allele frequencies were similar between cases and controls with no statistical significance. In the MTHFR gene none of the genotypes or allele frequency cannot show any association OR=1.281, p=.0.667, (95% CI=0.414-3.958) and OR=1.1.172, p=0.800¸ (95% CI=0.343-4.008). Similarly, the difference of T allele frequencies between patients and controls was not found any association. In conclusion, our finding indicates that the prevalence of G1691A, G20210A and C677T mutations in G6PD deficient individuals is not statistically different compared to normal subjects and G6PD is not associated with these thrombophilic mutations in Saudi population.     

The prevalence of factor V Leiden,prothrombin G20210A and methylenetetrahydrofolate reductase polymorphism C677T among G6PD deficient individuals from Western Iran

It has been suggested that the allele frequency of thrombophilic mutations is affected by glucose-6-phosphate dehydrogenase (G6PD) deficiency. The prevalence of thrombophilic mutations were studied in sixty G6PD deficient individuals including 57 males and three females with the mean age of 15 ± 3.08 and 110 age and sex matched healthy individuals consisted of 95 males and 15 females with the mean age of 16.19 ± 2.17 from the Kermanshah Province of Iran. Using a combination of PCR-RFLP technique, single strand conformation polymorphism (SSCP) analysis and DNA sequencing polymorphic G6PD mutations were identified. The factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T were detected by PCR-RFLP method using MnlI, HindIII and HinfI restriction enzymes, respectively. Three mutations, G6PD Mediterranean, G6PD Chatham and G6PD Cosenza were identified in 60 G6PD deficient individuals with highest prevalence of G6PD Mediterranean (91.6%). In G6PD deficient individuals the prevalence of factor V Leiden tended to be higher (5%) compared to healthy individuals (2.7%). The prevalence of prothrombin G20210A mutation in G6PD deficient individuals was 1.7%. However, in normal subjects the prevalence of this mutation was 2.7%. The frequency of T allele in G6PD deficient individuals were insignificantly higher (29.16%) than those in healthy individuals (26.8%). Our finding indicates that the prevalence of factor V Leiden, prothrombin G20210A and MTHFR C677T in G6PD deficient individuals is not statistically different compared to normal subjects and G6PD deficiency is not associated with these thrombophilic mutations in Western Iran.     

Rapid automated simultaneous screening of (G1691A) Factor V, (G20210A) prothrombin,and (C677T) methylenetetrahydrofolate reductase variants by multiplex PCR using fluorescence scanning technology

The Factor V Leiden mutation (G1691A), and mutations in the prothrombin (G20210A) and 5,10-methylenetetrahydrofolate reductase (C677T) genes are common hereditary risk factors associated with venous thrombosis. The aim of this study was to develop an automated, PCR-based genotyping assay for rapid simultaneous screening of these three mutations. We adapted multiplex PCR, using primer modifications to introduce cleavage sites for restriction endonucleases into the fragments bearing each of the mutations. The three mutations were analyzed in a single tube by fluorescence scanning. An internal digestion control was introduced to prevent false-negative results due to incomplete digestion or a total lack of digestion. DNA fragment analysis was carried out using an automated capillary electrophoresis instrument (ABI310). This reliable, efficient, easy-to-use assay can be applied to specimens from large clinical trials and epidemiological surveys.     

G20210A prothrombin gene mutation identified in patients with venous leg ulcers

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.     

Evaluation of Factor V G1691A,prothrombin G20210A,Factor XIII V34L,MTHFR A1298C,MTHFR C677T and PAI-1 4G/5G genotype frequencies of patients subjected to cardiovascular disease (CVD) panel in south-east region of Turkey

Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 ?675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66 %, respectively. No mutation was detected in 92 (1.95 %) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.     

Inherited thrombophilia genes in minorities

Mutations in several genes have recently been identified which predispose to thrombosis, specifically Factor V G1691A (Factor V Leiden), Prothrombin G20210A, and Methylene tetrahydrofolate reductase (MTHFR) C677T. The prevalence of these genes in European populations has been studied, but there is little data on their prevalence in minorities. Samples from a predominantly African-American population were analyzed for these mutations. While the G20210A mutation in the prothrombin gene and homozygosity for the C677T mutation of the MTHFR were not found in African-Americans, it appears that the carrier rate for the MTHFR C677T among Hispanics may be higher than in other reported groups.     

Causal Relationship of Susceptibility Genes to Ischemic Stroke: Comparison to Ischemic Heart Disease and Biochemical Determinants

Interrelationships between genetic and biochemical factors underlying ischemic stroke and ischemic heart disease are poorly understood. We: 1) undertook the most comprehensive meta-analysis of genetic polymorphisms in ischemic stroke to date; 2) compared genetic determinants of ischemic stroke with those of ischemic heart disease, and 3) compared effect sizes of gene-stroke associations with those predicted from independent biochemical data using a mendelian randomization strategy. Electronic databases were searched up to January 2009. We identified: 1) 187 ischemic stroke studies (37,481 cases; 95,322 controls) interrogating 43 polymorphisms in 29 genes; 2) 13 meta-analyses testing equivalent polymorphisms in ischemic heart disease; and 3) for the top five gene-stroke associations, 146 studies (65,703 subjects) describing equivalent gene-biochemical relationships, and 28 studies (46,928 subjects) describing biochemical-stroke relationships. Meta-analyses demonstrated positive associations with ischemic stroke for factor V Leiden Gln506, ACE I/D, MTHFR C677T, prothrombin G20210A, PAI-1 5G allele and glycoprotein IIIa Leu33Pro polymorphisms (ORs: 1.11 – 1.60). Most genetic associations show congruent levels of risk comparing ischemic stroke with ischemic heart disease, but three genes—glycoprotein IIIa, PAI-1 and angiotensinogen—show significant dissociations. The magnitudes of stroke risk observed for factor V Leiden, ACE, MTHFR and prothrombin, but not PAI-1, polymorphisms, are consistent with risks associated with equivalent changes in activated protein C resistance, ACE activity, homocysteine, prothrombin, and PAI-1 levels, respectively. Our results demonstrate causal relationships for four of the most robust genes associated with stroke while also showing that PAI-1 4G/5G polymorphism influences cardiovascular risk via a mechanism not simply related to plasma levels of PAI-1 (or tPA) alone.     

FV-Leiden- und Prothrombin-G20210A-Mutation

Factor V Leiden mutation and the prothrombin G20210A variant are the most common thrombophilic risk factors identified so far, with incidences of 2–4% and 1%, respectively. While the former is associated with the APC resistence phenotype, the prothrombotic phenotype of the prothrombin G20210A variant remains unclear. The presence of each of the mutations increases the risk of venous thromboembolism. However, the risk of recurrent venous thromboembolism is not significantly enhanced. Testing for both prothrombotic mutations can confirm the clinical diagnosis of thrombophilia but has no effect on the anticoagulant management of these patients.     

Insight into the role of CYBA A640G and C242T gene variants and coronary heart disease risk. A case-control study

The CYBA gene variants have been inconsistently associated with coronary heart disease (CHD) risk. A case-control study was conducted genotyping 619 subjects to explore the contribution of C242T and A640G to CHD risk in the population. A significant risk was found associated with GG homozygosity (odds ratio (OR) 2.132, 95% confidence interval, 1.113-4.085). The C242T variant was associated with CHD risk in women. Bias due to population stratification was analysed. Phenotype changes linked to these polymorphisms were evaluated. Superoxide measurements revealed higher production as indicated by the presence of the G and T alleles. Differences in mRNA concentration in heterozygous A640G samples were analysed. Higher levels of G allele mRNA compared with A allele mRNA were found. NAD(P)H oxidase p22phox sub-unit expression was evaluated with Western blot. Experiments revealed a gradual relationship in p22phox protein expression according to genotypes of the analysed variants. Those GG TT double homozygous showed increased p22phox protein expressions regarding AA CC double homozygous. This study has demonstrated increased expression and activity of the NAD(P)H system components during atherogenesis and the results could help explain the relevance of the A640G variant as a CHD marker.     

Screening of mitochondrial mutations in Saudi women diagnosed with gestational diabetes mellitus: A non-replicative case-control study

IntroductionAmong metabolic disorders, gestational diabetes mellitus (GDM) is specified as hyperglycemia caused by glucose or carbohydrate intolerance defects. GDM is distinguished by oxidative stress, and has been connected to mitochondrial dysfunction. Previous studies have documented the relation between A12026G, A8344G and A3243G mutations in ND4, tRNA^Leu(UUR), and tRNA^Lys genes in different modes of diabetes.AimThe purpose of this study was to investigate into the relationship between GDM women and common mitochondrial mutations including A12026, A8344G, and A3243G in Saudi women.MethodsIn this case-control study, we have opted 96 GDM and 102 non-GDM pregnant women and DNA was extracted using EDTA blood and based on specific primers, Polymerase Chain Reaction was followed and then Restriction Fragment Length Polymorphism (RFLP) analysis was performed. Restriction enzymes was cross-checked with Lambda DNA and 10% of the purified PCR products were performed the Sanger sequencing analysis to reconfirm the RFLP analysis of the studied results.ResultsNone of the heterozygous and homozygous mutations were not observed in our study. All the subjects were turned to be homozygous normal genotypes.ConclusionThis study confirms that A12026, A8344G, and A3243G mutations have no role in the Saudi women with GDM.     

Inherited genetic markers for thrombophilia in northeastern Iran (a clinical-based report)

Background:

Thrombophilia is a main predisposition to thrombosis due to a procoagulant state. Several point mutations play key roles in blood-clotting disorders, which are grouped under the term thrombophilia. These thrombophilic mutations are methylenetetrahydrofolate reductase (MTHFR, C677T, and A1298C), factor V Leiden (G1691A), prothrombin gene mutation (factor II, G20210A), and plasminogen activator inhibitor (PAI). In the present study, we assessed the prevalence of the above thrombophilia markers in patients with recurrent pregnancy loss or first and second trimester abortions, infertility, and failed in vitro fertilization (IVF).

Methods:

This study was conducted among 457 cases those were referred to detect the inherited genetic markers for thrombophilia. Markers for MTHFR, Factor II, and Factor V were assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and PAI was assessed by Amplification Refractory Mutation System (ARMS-PCR).

Results:

Two hundred sixty cases (56.89%) were diagnosed as having at least one thrombophilia marker, whereas 197 cases (43.11%) had no thrombophilia markers and were normal.

Conclusion:

According to the current study, the pattern of abnormal genetic markers for thrombophilia in northeastern Iran demonstrates the importance of genetic evaluations in patients who show clinical abnormalities with recurrent spontaneous abortion (RSA) or other serious obstetric complications.Key Words: Thrombophilia, Thrombophilic markers, MTHFR, Factor II, Factor V, PAI     

Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type

Background:ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.Methods:We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction.Results:The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3–1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0–2.5) for heterozygous participants and 7.0 (95%CI 4.8–10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2–1.9) for heterozygous participants and 11 (95% CI 2.8–44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p < 0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0.Interpretation:ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.Genome-wide association studies have reported that ABO blood type locus is an important genetic determinant of venous and arterial thrombosis,^1,2 leading to renewed interest in the association between ABO blood type and venous and arterial thrombosis. This challenges conventional thoughts on genetic screening for thrombophilia, which presently does not include ABO blood type.Individuals with an A or B blood type have an increased risk of venous thromboembolism and myocardial infarction compared with individuals with O blood type.^3–6 Earlier studies concluded that ABO antigen expression determines von Willebrand factor levels;^7–11 however, recent findings from genome-wide association studies suggest that ABO antigens may also exert their effect through other pathways.^12–16 Both factor V Leiden R506Q and prothrombin G20210A mutations have been consistently associated with increased risk of venous thrombosis but not consistently associated with the risk of arterial thrombosis.^17–19In this study, we tested the hypothesis that ABO blood type, alone and in combination with the factor V Leiden R506Q and prothrombin G20210A mutations, is associated with the risk of venous thromboembolism and myocardial infarction in the general population.     

MTHFR C 677T mutation and 4G/5G PAI-1 polymorphism in patient with polycystic ovarian syndrome

Combined oral contraceptives (Ocs) are the most commonly used androgen suppressors and the treatment of choice for menstrual dysfunction in women with polycystic ovarian syndrome (PCOs). Although OCs have remained popular due to their convenience and effectiveness, there have been continuing concerns about adverse effects. The OCs have long been known to incur and increased risk of venous thromboembolism especially in carriers of common inherited thromboembolic defects. Factor V Leiden, prothrombin factor G20210A polymorphism, MTHFR (C677T) mutation and 4G/5G polymorphism of the PAI-1 gene account for the majority of thromboembolic events in association with oral contraceptive use. The aim of the article is to present woman with unrecognized inherited thrombophilia who was treated with OCs due to PCOs signs.     

Gaucher disease: gene frequencies in the Ashkenazi Jewish population.

DNA from over 2,000 Ashkenazi Jewish subjects has been examined for the four most common Jewish Gaucher disease mutations, which collectively account for about 96% of the disease-producing alleles in Jewish patients. This population survey has made possible the estimation of gene frequencies for these alleles. Eighty-seven of 1,528 individuals were heterozygous for the 1226G (N370S) mutation, and four presumably well persons were homozygous for this mutation. The gene frequency for the 1226G allele was calculated to be .0311, and when these data were pooled with those obtained previously from another 593 Jewish subjects, a gene frequency of .032 with a standard error of .004 was found. Among 2,305 normal subjects, 10 were found to be heterozygous for the 84GG allele, giving a gene frequency of .00217 with a standard error of .00096. No examples of the IVS2(+1) mutation were found among 1,256 samples screened, and no 1448C (L444P) mutations were found among 1,528 samples examined. Examination of the distribution of Gaucher disease gene frequencies in the general population shows that the ratio of 1226G mutations to 84GG mutations is higher than that in the patient population. This is presumed to be due to the fact that homozygotes for the 1226G mutation often have late-onset disease or no significant clinical manifestations at all. To bring the gene frequency in the patient population into conformity with the gene frequency in the general population, nearly two-thirds of persons with a Gaucher disease genotype would be missing from the patient population, presumably because their clinical manifestations were very mild.     

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and β-fibrinogen −455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9–49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1–0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01–0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, β fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.     

The G1691A mutation of the coagulation factor V gene (factor V Leiden) is rare in Chinese: an analysis of 618 individuals

To understand the allele frequency of the G1691A mutation of the coagulation factor V gene (factor V Leiden) in Chinese, 618 Chinese individuals, including 54 cases with venous thrombosis, were analyzed. Only one case in the control group was heterozygous for the 1691G allele and the 1691A allele. Our data suggest that the factor V Leiden is rare in Chinese. Received: 5 February 1996 / Revised: 20 March 1996