Thrombophilic Gene Polymorphisms Research Articles

The Presence of PAI-1 4G/5G and ACE DD Genotypes Increases the Risk of Early-Stage AVF Thrombosis in Hemodialysis Patients

Background: In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Methods: Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Results: Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x2 = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. Conclusion: PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

Inherited thrombophilia in infertile women: implication in unexplained infertility

Many studies evaluating a possible relationship between inherited thrombophilia and the etiology of unexplained infertility have been performed recently. No significant difference in the prevalence of three genetic mutations associated with the increased risk of thrombophilia (Factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677 T) was found in 100 infertile women with unexplained infertility when compared with 200 control fertile women without an infertility history.

FP23-TU-05 Coagulation factor gene polymorphisms in puerperal cerebral venous thrombosis

Purpose: Puerperal cerebral venous thrombosis (PCVT) is a common cause of stroke in young women in India, where it is 10–12 times more common than in the West. The etiology of PCVT is not yet clear. Various thrombophilic gene polymorphisms have been reported to be associated with venous thrombosis in Caucasians. Published literature on their role in the etiology of PCVT is scarce. Hence, our aim was to evaluate the role of common single nucleotide thrombophilic gene polymorphisms such as prothrombin G20210>A, factor V Leiden G1691>A, factor V A4070>G and factor VII R353>Q as risk factors for PCVT. Methods: After approval by the NIMHANS Human Ethics committee, we investigated 100 female patients with a confirmed diagnosis of PCVT and 102 age-matched clinically normal women with no postnatal complications. Restriction length fragment polymorphism (RFLP) technique was used for identifying the presence or absence of the polymorphisms. Results: Factor V Leiden (OR=0.50, 95%CI = 0.09–2.79, p = 0.683), Factor V A4070G (OR=1.17, 95%CI = 0.49–2.75, p = 0.567) and factor VII R353Q (OR=1.55, 95%CI = 0.89–2.70, p = 0.243) polymorphisms were not significantly associated with PCVT. Moreover, coinheritance of these polymorphisms did not confer an increased risk for PCVT (OR=1.17, 95%CI = 0.53–2.61, p = 0.696). Prothrombin G202010A mutation was found to be absent in our population. Conclusion: We conclude that factor V Leiden, factor V A4070G and factor VII R353Q polymorphisms, though present in the Indian population, are not significantly associated with increased risk for PCVT in Indian women.

Thrombophilic gene polymorphisms are risk factors for unexplained infertility

Earlier studies have shown inherited thrombophilia to be a risk factor for recurrent implantation failure, raising the question of whether this risk is related to the underlying cause of unexplained infertility or to the mechanisms involved in the implantation process. When nine thrombophilic gene polymorphisms were compared among 92 women with the diagnosis of unexplained infertility and 60 fertile control women, women with a history of unexplained infertility displayed a higher prevalence of MTHFR C677T polymorphisms than control women.

ORIGINAL ARTICLE: Comparison of Thrombophilic Gene Mutations Among Patients Experiencing Recurrent Miscarriage and Deep Vein Thrombosis

Problem Inherited thrombophilia has been shown to be a risk factor for cardiovascular disease including deep venous thrombosis as well as reproductive disorders including recurrent pregnancy loss. We have previously reported three out of the 10 thrombophilic mutations studied, plasminogen activator inhibitor‐1 (PAI‐1) 4G/5G, factor XIII V34L, and homozygous MTHFR C667T, correlated significantly with recurrent pregnancy loss compared with controls. This study was undertaken to compare the frequencies of nine inherited thrombophilias among women with a history of recurrent pregnancy loss with individuals experiencing deep venous thrombosis and fertile controls.Method of study Six hundred thirty‐four participants including 550 women with a history of recurrent pregnancy loss, 43 individuals with deep vein thrombosis and 41 fertile women without a history of recurrent miscarriage. All participants had buccal swabs taken for DNA analyses of nine gene polymorphisms including factor V G1691A, factor V H1299R (R2), factor II Prothrombin G20210A, factor XIII V34L, β‐fibrinogen −455G>A, PAI‐1 4G/5G, human platelet antigen 1 a/b (L33P), MTHFR C677T, MTHFR A1298C. Frequencies of thrombophilic gene polymorphisms were compared among the three populations studied.Results Individuals with a history of DVT had a significantly higher frequency of all of the polymorphisms studied compared with women experiencing a history of recurrent pregnancy loss and the fertile controls. The frequencies of mutations for V34L and PAI‐1 4G/5G were significantly increased among women experiencing recurrent pregnancy loss compared with controls. The most prevalent polymorphisms were factor XIII V34L and PAI‐1 4G/4G for both individuals with a history of deep vein thrombosis and recurrent pregnancy loss compared with controls.Conclusion Screening for risk factors for inherited thrombophilia with only polymorphisms for factor V von Leiden, factor II prothrombin and MTHFR may be missing the more prevalent identifiers of jeopardy.

Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension

Idiopathic portal hypertension (IPH) is characterized by non-cirrhotic presinusoidal intrahepatic portal hypertension. The etiopathogenesis of the disease is poorly understood. Obliteration with microthrombosis of the small portal vein branches may lead to lesions underlying portal hypertension. We aimed to put forward a comprehensive thrombophilic mutation profile in IPH and its probable contribution to pathogenesis. Eleven patients and 12 controls were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen -455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. We also evaluated some blood parameters and protein C, protein S, AT-III levels using commercially available assays. IPH patients and controls were similar in respect to gender distribution (P = 1.000). Mean age was 31.2 in patients and 29.1 in controls (P = 0.622). Pica history was present in 54.5% of the patients. Mean protein C and AT-III levels were lower in patients than that of controls (P = 0.002 and 0.001, respectively). Factor XIII V34L, PAI-1, GPIIIa L33P, MTHFR C677T and MTHFR A1298C frequencies of genetic polymorphisms were found to be significantly higher among patients than that of controls. Apolipoprotein E2/E3/E4 analysis showed an inverse relationship with IPH when E2 plus E4 compared with E3. A higher frequency of Beta-Fibrinogen -455G-A mutation was observed in patients, but this difference did not reach a statistical significance. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphisms in IPH. The data support a possible pathogenetic role in IPH, at least by some of the prothrombotic mutations. In order to confirm or refuse this proposal, a larger cohort of patients is needed.

Gene Polymorphism Analysis Related to the Development of Deep Vein Thrombosis

Purpose: To determine if the presence of thrombophilic genes affects the development of deep vein thrombosis after total knee arthroplasty (TKA). Materials and Methods: One hundred and forty consecutive patients who underwent primary total knee arthroplasty were enrolled in this study. Preoperatively, all the patients were evaluated for general and hematological risk factors, as well as associated thrombophilic gene polymorphisms. Molecular genetic testing was carried out to detect the following thrombophilic gene polymorphisms: the factor V Leiden mutation, prothrombin promoter G20210A mutation, methylenetetrahydrofolate reductase (MTHFR) C677T, and the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism. Results: Deep vein thrombosis was observed in 48 (34%) patients. Regarding the genetic factors, no mutations in factor V Leiden or prothrombin promoter G20210A were detected in any patient regardless of whether they had DVT. The T677T and C677T genotypes of the MTHFR gene had no effect on the development of DVT compared with the C677C genotype. Regarding the PAI-1 gene, the presence of 4G/4G was not associated with an increased risk of DVT. In addition, there was a similar prevalence of the 4G allele in the DVT patients (77%) and controls (84%). Conclusion: Thrombophilic gene polymorph isms do not appear to play an important role in the development of deep vein thrombosis. Therefore, screening tests for these genes will not be useful in determining the risk of deep vein thrombosis in our ethnic patients.

The prothrombin gene G20210A variant and puerperal cerebral venous and sinus thrombosis in South Indian women

Pregnancy and puerperium raise the risk of thrombotic events, and these risks are likely to be increased in women who are carriers of thrombophilic gene polymorphisms. Prothrombin G20210A variant is reported to be the second most frequent prothrombotic polymorphism in Caucasians. Our aim was to determine the prevalence of this variant in south Indian women and examine its association with cerebral venous and sinus thrombosis occurring during puerperium. We investigated 96 women with puerperal cerebral veno-sinus thrombosis (CVT) and 103 age-matched women with no post-partum complications. We used restriction fragment length polymorphism analysis to identify their genotypes. The prothrombin G20210A variant was not detected in either the CVT patients or the healthy control subjects. Our study on a large series of patients with puerperal CVT shows that the prothrombin G20210A variant is not present in south Indian women and is not associated with puerperal CVT. This study also highlights the fact that there are racial differences in the risk factors for thrombosis, which should be considered when investigating these patients.

Role of Thrombophilic Gene Polymorphisms in Branch Retinal Vein Occlusion

Branch retinal vein occlusion (BRVO) is a common cause of severe visual loss. Numerous risk factors, including arterial hypertension, diabetes mellitus, and arteriosclerosis, have been identified. Gene polymorphisms affecting hemostasis may also play a role in the pathogenesis of BRVO. The present study was therefore done to determine the prevalence of genetic polymorphisms in factors implicated in hypercoagulability among patients with BRVO. Retrospective case-control study. The study cohort consisted of 294 patients with BRVO and 294 control subjects, matched for age and gender. Determination of genotypes was done by allele-specific digestion of polymerase chain reaction products, or by 5' exonuclease assay (TaqMan). Genotypes of factor V R506Q (factor V Leiden), prothrombin 20210G>A, fibrinogen beta -455G> A, factor XII (FXII) 46C>T, and ITGA2 807C>T (platelet glycoprotein Ia [GPIa] 807C>T) and ITGB3 L59P (platelet GPIIIa PlA1/PlA2) polymorphisms. Genotype distributions of the investigated gene polymorphisms did not differ significantly between patients and control subjects. In contrast, significantly increased prevalences of arterial hypertension and hypercholesterolemia were found among patients with BRVO. In a logistic regression analysis, the presence of arterial hypertension was associated with an odds ratio (OR) of 2.32 (95% confidence interval [CI], 1.62-3.32), whereas hypercholesterolemia yielded an OR of 2.54 (95% CI, 1.74-3.70) for BRVO. Our data indicate that the prevalences of the investigated gene polymorphisms do not differ significantly in patients with BRVO and control subjects. This suggests that these polymorphisms are not major risk factors for BRVO.