The FXIIIVal34Leu, common and risk factors of venous thrombosis in early middle-age Costa Rican patients.

In this study, eight common polymorphisms associated with venous thrombosis (VT) and thrombophilia factors were analyzed in a Costa Rican case-control study. With the use of polymerase chain reaction (PCR) methods the polymorphisms were detected in 120 patients and 133 controls (mean age <40 years old). It was concluded that a high level of fibrinogen, antiphospholipid antibodies, family history, and the genotype 34LeuLeu of FXIII OR 0.42 (0.20-0.89) showed a significant effect on the risk of VT. Associations between the risk of VT and genetic polymorphisms have been established. Some of these polymorphisms are highly prevalent in Caucasians, but there is a significant geographic variation in their prevalence among different populations. The results of this study support the protective effect of FXIII Val34Leu polymorphism in VT. These findings are consistent with previous reports that included other populations.

Common polymorphisms and cardiovascular factors in patients with myocardial infarction of Costa Rica

Eight common polymorphisms of known myocardial infarction (MI)risk factors (factor V Leiden (FVL), factor V HR2 (FVHR2), factor II 20210G>A (FII), factor VII IVS7 (FVII IVS7), factor VII Arg353Gln (FVII), factor XIII Val34Leu (FXIII), Methylenetetrahydrofolate reductase C677T (MTHFR), Angiotensin Converting Enzyme (ACE))and environmental risk factors were analyzed in a MI patients of Costa Rica.This case-control study included 186 MI subjects,95 of them <45 years and 201 age and sex matched controls.With the use of PCR method the polymorphisms were detected and through interviews additional information was collected.Hypercholesterolemia and smoking were associated with a significant risk in younger patients.High fibrinogen level was an important risk factor and interaction with smoking was detected.Mainly,the genotype 34LeuLeu of FXIII showed significant protective effect,(OR 0.32,95%CI 0.13-0.80)while the other polymor- phisms showed no significant difference between the cases and the controls.Carriers of FVII (OR 2.75,95%CI 1.07-7.02)and FXIII (OR 4.20,95%CI 2.03-8.67)polymorphisms showed interaction with fibrinogen in the sta- tistical analysis.It was concluded that there was an important interaction between the common risk factors and the polymorphisms (FVII;FXIII)in the development of MI.This is one of the first reports in a Latin-American population dealing with these molecular markers and MI.

Se estudiaron ocho polimorfismos comunes asociados como factores de riesgo para el infarto al miocardio (IM):factor V Leiden (FVL),factor VHR2 (FVHR2), factor II 20210G>A (FII),factor VII IVS7 (FVII IVS7), factor VIIArg353Gln (FVII),factor XIIIVal34Leu (FXIII), metilentetrahidrofolato reductase C677T (MTHFR), enzima convertidora de la angiotensina (ACE) y factores ambientales de riesgo,en pacientes costarricenses.Este es un estudio de casos y controles,donde participan 186 pacientes,95 de ellos con edades <45 años y 201 sujetos controles.Se utilizó la técnica de reacción en cadena de la polimerasa (PCR)y por medio de entrevistas personales se recolectó información epidemiológica adicional.Se encontró que la hipercolesterolemia y el fumado estan asociados como factores de riesgo en los pacientes jóvenes.Niveles elevados del fibrinógeno fueron detectados como un factor de riesgo importante y se observo interacción entre fumado y estos valores aumentados de fibrinógeno. El genotipo 34LeuLeu del FXIII presentó un efecto protector significante mientras que los otros polimorfimos estudiados no mostraron diferencia estadísticamente significativa entre los casos y controles. Los polimorfismos del FVII y FXIII demostraron interación con el fibrinógeno,según el análisis estadístico aplicado. Se evidencia, la interación entre factores de riesgo común y ciertos polimorfismos (FVII;FXIII)en la patogénesis del IM.Este es uno de los primeros informes sobre estos marcadores moleculares y su asociación con IM en una población latinoamericana.

Common polymorphisms and cardiovascular factors in patients with myocardial infarction of Costa Rica.

Eight common polymorphisms of known myocardial infarction (MI) risk factors (factor V Leiden (FVL), factor V HR2 (FVHR2), factor II 20210G > A (FII), factor VII IVS7 (FVII IVS7), factor VII Arg353Gln (FVII), factor XIII Va134Leu (FXIII), Methylenetetrahydrofolate reductase C677T (MTHFR), Angiotensin Converting Enzyme (ACE)) and environmental risk factors were analyzed in a MI patients of Costa Rica. This case-control study included 186 MI subjects, 95 of them < or = 45 years and 201 age and sex matched controls. With the use of PCR method the polymorphisms were detected and through interviews additional information was collected. Hypercholesterolemia and smoking were associated with a significant risk in younger patients. High fibrinogen level was an important risk factor and interaction with smoking was detected. Mainly, the genotype 34LeuLeu of FXIII showed significant protective effect, (OR 0.32, 95% CI 0.13-0.80) while the other polymorphisms showed no significant difference between the cases and the controls. Carriers of FVII (OR 2.75, 95% CI 1.07-7.02) and FXIII (OR 4.20, 95% CI 2.03-8.67) polymorphisms showed interaction with fibrinogen in the statistical analysis. It was concluded that there was an important interaction between the common risk factors and the polymorphisms (FVII; FXIII) in the development of MI. This is one of the first reports in a Latin-American population dealing with these molecular markers and MI.

[Homocysteinemia and its relationship with the methylentetrahydrofolate reductase polymorphism in various ethnic groups from western Venezuela]. / La homocisteinemia y su relación con el polimorfismo de la metilentetrahidrofolato reductasa en varios grupos etnicos del occidente de Venezuela.

The prevalence of hyperhomocysteinemia and C677T MTHFR polymorphism was studied in various ethnic groups from Western Venezuela (60 Wayuu Indians, 42 italian immigrants and 77 Venezuelan mestizos) in relation with the prevalence of hyperhomocysteinemia and the C677T MTHFR polymorphism. Homocysteinemia was determined by polarized fluorescence immunoassay in an IMX system, serum folate was measured by radioimmunoanalysis and the MTHFR genotype was determined by PCR and restriction analysis. Hyperhomocysteinemia was defined as a value over 2 SD above the mean value for normal MTHFR (CC677) in each group. The prevalence of MTHFR variants (C677T and 677TT) was elevated in all ethnic groups (78% among the wayuu, 76% among Italians and 63% among mestizos) with a significant association between the concentrations of homocysteine and the levels of serum folate among the wayuu (p < 0.0001) and the mestizos (p < 0.001) only. Hyperhomocysteinemia was associated with MTHFR variants in 23% of the wayuu (OR: 6.17, CI 95: 0.74-51.36), 9.5% of the Italians (OR: 0.93, CI 95: 0.085-10.10) and 20.7 of the Venezuelans mestizos (OR: 5.2, CI 95: 1.08-24.90, p > 0.03). There was no relationship between hyperhomocysteinemia and folate deficiency in any of the groups studied. In conclusion, despite a high prevalence of C677T MTHFR variants in these ethnic groups of western Venezuela, the lack of no evidence of hyperhomocysteinemia combined with folate deficiency may imply that the nutritional status of these groups plays an important role in the control of hyperhomocysteinemia as a risk factor for cardiovascular disease.

La homocisteinemia y su relación con el polimorfismo de la metilentetrahidrofolato reductasa en varios grupos étnicos del occidente de Venezuela / Homocysteinemia and its relationship with the methylentetrahydrofolate reductase polymorphism in various ethnic groups from western Venezuela

Con el propósito de establecer la prevalencia de la hiperhomocisteinemia y su relación con el polimorfismo de la metilentetrahidrofolato reductasa, se estudiaron tres grupos étnicos del Occidente de Venezuela, localizados en la región del Estado Zulia (60 individuos Wayuú en la alta Goajira venezolana, 42 inmigrantes italianos y 77 venezolanos mestizos). La homocisteína fue determinada por ensayo inmunoenzimático utilizando lámpara de flourescencia polarizada, el folato sérico fue medido por radioinmunoanálisis y el polimorfismo de la MTHFR se realizó mediante reacción en cadena de la polimerasa y análisis de restricción. Se encontró una alta proporción en las variantes de la MTHFR 677TT y C677TT en los indígenas wayuú (78 por ciento), italianos (76 por ciento) y mestizos venezolanos (63,6 por ciento), con asociación significativa entre los niveles altos de homocisteína y concentraciones menores de folato en los wayuú (p < 0,0001) y en los venezolanos mestizos (p < 0,001). Las variantes polimórficas de la MTHFR se asociaron con hiperhomocisteinemia en el 23,3 por ciento de los indígenas wayuú (OR: 6,17; IC 95: 0,74-51.36), el 9,5 por ciento de los italianos (OR: 0,93; IC 95: 0,085-10,10) y en el 20,7 por ciento de los mestizos venezolanos (OR: 5,2; IC 95: 1,08-24,90; p < 0,03). No se encontró asociación entre hiperhomocisteinemia y deficiencia de folato en ninguna de las poblaciones estudiadas. Se concluye que a pesar de una alta prevalencia de variantes para la MTHFR en los grupos étnicos estudiados, el factor nutricional juega un papel importante en el control de la hiperhomocisteinemia y sus posibles consecuencias cardiovasculares

Interaction between factor V Leiden and serum LDL cholesterol increases the risk of atherosclerosis.

OBJECTIVES: We investigated the association between the factor V Leiden gene variant and carotid atherosclerosis in a cross-sectional study and explored possible associations between this gene variant and coronary artery disease (CAD) in a case-control study. METHODS: The presence (n=1696) or absence (n=703) of carotid atherosclerosis were sonographically assessed among participants of the population-based Study of Health in Pomerania (SHIP). The case-control study included 1021 patients with severe CAD and 2791 healthy SHIP participants. The factor V Leiden gene variant was determined by PCR and MnlI digestion. RESULTS: Multivariable analyses revealed no independent association between the factor V Leiden gene variant per se and carotid atherosclerosis or CAD. In the cross-sectional study, there was an interaction between the factor V Leiden gene variant and serum LDL cholesterol in non-diabetics with respect to the risk of carotid atherosclerosis. In the case-control study a similar interaction was found for CAD. In both studies the atherosclerotic risk increased with rising serum LDL cholesterol concentrations in carriers of the factor V Leiden gene variant. CONCLUSION: The co-existence between the factor V Leiden gene variant and high serum LDL cholesterol is independently associated with the risk of atherosclerosis.

Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders.

In this study we investigated the influence of the presence of the factor V HR2 haplotype, defined by the factor V gene mutation H1299R (FV(HR2)), on thrombin generation. Measurements were performed in platelet-poor plasma of individuals with factor V(HR2) or factor V(Leiden) in comparison to a control group carrying none of these mutations. Coagulation was triggered by low concentrations of recombinant tissue factor in the presence of activated protein C. Thrombin generation was monitored by a fluorogenic substrate. The endogenous thrombin potential was calculated from the obtained curves. As a result we observed an increased thrombin generation both for individuals heterozygous and homozygous for FV(HR2). The level of endogenous thrombin potential is in the same range as in samples of patients heterozygous or homozygous for FV(Leiden). The results indicate that FV(HR2) plays a role as a risk factor for venous thrombosis in homozygous patients through an increased thrombin generation. The association between different clinical manifestations in individuals with FVII deficiency and endogenous thrombin potential and the presence of FV(HR2) was studied.

Prevalence of eight molecular markers associated with thrombotic diseases in six Amerindian tribes and two African groups of Costa Rica.

Individuals belonging to six different Amerindian tribes and two African groups of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV HR2), Factor II 20210G>A (FII), the methylenetetrahydrofolate reductase (MTHFR), factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE). Clear differences in the prevalence were found and are first reported. The prevalence of some of the established genetic risk factors was low in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR, FVHR2) had an extremely high prevalence. People of African origin carried very rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest reported. Concerning the protective factors, the QQ genotype of FVII R353Q was absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal heterogeneity was observed that may reflect the evolutionary history of these tribal groups and their admixture with other populations.

Factor V Leiden and the risk of stillbirth in a German population.

An association between the factor V Leiden variant and an increased risk of pregnancy loss has been reported. Most previous studies were performed with clinically recruited patients and controls. This approach may cause selection bias. The present analysis was performed with the aim to investigate the association between the factor V Leiden mutation and the risk of stillbirth in a population-based sample. The Study of Health in Pomerania (SHIP) is a survey that was carried out in North East Germany. A random sample from the population aged 20 to 79 years was taken. The total SHIP population comprised 4,310 participants. The presence of the factor V Leiden variant was determined by PCR and Mnl I digestion. The presence of the factor V Leiden variant was neither associated with the number of pregnancies nor with the number of children per women. Data from 1,768 females who had at least one pregnancy with known outcome was available for the present analysis. Seventy-three women (4.1%) reported at least one stillbirth. Women with and without the factor V Leiden mutation did not differ with respect to the number of women with at least one stillbirth (OR for factor V Leiden variant 1.57; 95%-CI 0.76 - 3.25). Furthermore, the number of women with two or more stillbirths, the number of stillbirths per affected woman and the number of stillbirths per number of pregnancies per woman was similar between both genotype groups. In conclusion, there is no association between the factor V Leiden mutation and the risk of stillbirth in a representative population sample.