The present study aimed to evaluate the impact of factor V Leiden (FVL) polymorphism within the reproductive problems encountered by patients with polycystic ovary syndrome (PCOS). A total of 92 female patients with PCOS and 101 healthy controls were included in the study. Clinical and laboratory parameters were examined. The full history of each patient was taken. Single nucleotide polymorphism rs6025 in F5 was genotyped in PCOS patients and compared to the genotype frequency of the healthy controls. The data were analysed for correlation with infertility and pregnancy loss in PCOS patients. The prevalence of FVL polymorphism was higher, however not significantly, in PCOS patients compared to that of the control group (respectively OR=2.238, 95 % CI 0.777±6.449, p=0.104). The carriers of FVL polymorphism showed a higher rate of primary infertility (30.0% versus 12.5%, OR=3.143, 9 % CI 0.686±14.388, p=0.047) and their total reproductive failure rate was higher (60.5% versus 47.2%, OR=1.819, 95% CI 0.632±9.259, p=0.117). Carriage of FVL polymorphism in PCOS patients is associated with primary infertility and a presumed cause of the further investigations needed to understand the impact of FVL on PCOS. Carriage of FVL polymorphism in PCOS patients is associated with a higher rate of primary infertility, which draws attention to the role of this factor in the aetiology of the PCOS-related subfertility. Further investigations are needed to understand the impact of FVL on PCOS.
Fetuin-A is a major plasma glycoprotein released mainly by the liver. Its functions include inhibition of the activity of insulin receptor, regulation of response to inflammation, inhibition of calcified matrix metabolism and ectopic mineralization, etc. Three major functional domains of fetuin-A have been identified: one similar to the Ca-binding domains, one inhibiting cysteine protease, and a domain with high affinity to insulin receptor. The fetuin-A molecule may be considered as a highly pleomorphic protein with an important impact in a variety of clinically expressed metabolic and pathological processes. It could be used as a marker in clinical practice in the future.
Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.
The incidence of deep venous thrombosis (DVT) depends on the specific genotype, inheritance of prothrombotic polymorphisms and the influence of environmental risk factors. Rs1799889(-) polymorphism in the promotor of PAI-1 gene has been described as a risk factor for hypercoagulable state. Objective: To evaluate the contribution of thrombophilic rs1799889 (-) in the promotor of PAI-1 gene on the incidence of DVT in women and men in groups below and above 45 years of age. Тhere was significantly higher rs1799889 (-) polymorphism carriage among female patients with DVT vs controls (Chi squared =5.506, OR=2.170, p=0.021) but not in male patients (Chi squared =0.090 OR=1.147, p=0.825). A significant contribution of rs1799889 (-) polymorphism to early onset of the disease was found in female patients aged 45+ and carriers of the polymorphism (Chi squared =7.476, p=0.006), but not in young women.
Platelet activation is a complex process in which platelet reorganization takes place associated with changes in the cell shape, topology, membrane elasticity and microparticle production. The aim of this study was to investigate the changes/aberrations in the platelet activity, elasticity and morphology in healthy subjects, carriers of A allele of prothrombin G20210A polymorphism. Blood samples from 18 healthy subjects were used for platelet analysis by force-mode atomic force microscopy. Restriction analysis was used to investigate the carriage of G20210A polymorphism in the prothrombin gene. Flow- cytometry was applied to evaluate platelet activation. Young’s modulus of the plasma membranes of platelets derived from healthy subjects, carriers of variant A allele of prothrombin 20210G>A polymorphism (407±69 kPa) is two times higher than the one determined for noncarriers (195.4±48.7 kPa; p<0.05). The background activity of platelets measured as an interrelation of Cd41/Cd61 and CD62 by flow cytometry was also higher in carriers of variant A allele of prothrombin 20210G>A polymorphism (5.0%) than in non-carriers (1.3%). Platelets isolated from healthy carriers of variant A allele of prothrombin 20210G>A polymorphism exhibited a higher level of activity and a higher degree of stiffness at the stage of spreading as compared to platelets from noncarriers.
Administration of antiplatelet therapy Aspirin and Clopidogrel (CLP) is a corner stone inpatients with Acute Coronary Syndrome (ACS) undergoing Percutaneous Coronary Intervention (PCI) with/without stent implantation. The CYP2C19*2 allele is the most important genetic variant determining response to CLP. We aim to investigate frequency of CYP2C19*2 polymorphism in patients with ACS and significance for the individual response to CLP therapy. The preliminary data of a study including a total of 120 patients with ACS undergoing PCI with stent placement and treated with dual antiplatelet therapy (CLP and Aspirin) are presented. So far 18 patients (41-81 year age) are tested for CYP2C19*l/*2 polymorphisms. The genotype CYP2C19*1/*1; CYP2C19*l/*2 and CYP2C19*2/*2 is demonstrated in 50%, 33%, 17% respectively, of the patients. The established frequency of CYP2C 19*2 allele (33%) is significantly higher (x2=5.220; p=0.022) than in healthy Bulgarian individuals (16%). In-stent thrombosis have developed 3 (17%) of patients: 2 are C YP2C19* l/*2 carriers, and 1 - homozygous CYP2C19*2/*2. The preliminary data demonstrate high prevalence of CYP2C19*2 polymorphism in patients with ACS and point to significance of the variant for CLP therapy. Further extension of the study with larger samples and monitoring of the patients are required to determine the effects of the polymorphism on the prognosis for major adverse cardiovascular events.