Rosanna Fiore - Academia.edu (original) (raw)

Papers by Rosanna Fiore

Clinical laboratory

In the last decades we found many data concerning the association between a hypercoagulable state... more In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). Although first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Now, emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. This review will be focused on the recent knowledge between thrombophilia, hypercoagulable state, RPL, VTE and future perspectives.

Background: Acute myocardial infarction (AMI) in young women represent an extreme phenotype assoc... more Background: Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. Methods: We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy).

Journal of translational medicine, Jan 22, 2004

BACKGROUND: Congenital thrombotic risk factors, oncological diseases and its therapies have been ... more BACKGROUND: Congenital thrombotic risk factors, oncological diseases and its therapies have been related to an increased occurrence of upper extremities deep venous thrombosis (UEDVT). PATIENTS AND METHODS: We studied seven patients bearing lymphoma (one Hodgkin's and six non-Hodgkin's) who developed UEDVT, one at diagnosis and six during chemotherapy (two of these six cases had implantation of a central venous catheter and four received Growth Colony Stimulating Factors in addition to chemotherapy). Patients were screened for: factor V G1691A (Leiden), prothrombin G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T mutations and antithrombin III, proteins C and S plasma activity. RESULTS: All patients were wild-type homozygotes for G20210A. One was heterozygote for factor V G1691A, the other 6 were wild-type homozygotes. Three of the 7 patients were homozygotes and 2 heterozygotes for the MTHFR mutation; the remaining 2 were wild-type homozygotes. Clotting inhibitor...

Thrombosis Research, 2014

Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue-type pla... more Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue-type plasminogen activator in plasma and the most important regulator of the fibrinolytic pathway. The 4G/5G polymorphism (rs1799889) in the PAI-1 promoter is associated with altered PAI-1 transcription. We have identified a new 4G/5G allele, in which a T is inserted near the 4G tract or replaces a G in the 5G tract, forming a T plus 4G (T4G) region. This new variant was first identified in two women, one had experienced juvenile myocardial infarction, the other repeated miscarriage; both had increased PAI-1 plasma activity. In view of the important influence of this promoter region on PAI-1 protein plasma level, we performed in vitro evaluation of the effects of the T4G variant on the transcription activity of the PAI-1 gene promoter. In silico prediction analysis showed that presence of the T4G allele disrupts the E-Box region upstream of the T4G variant, altering the affinity of the target sequence for E-Box binding factors like upstream stimulatory factor-1 (USF-1). Basal T4G promoter activity was 50% higher compared to 4G and 5G variants, but it was less stimulated by USF-1 overexpression. We also analyzed the effects of IL-1β and IL-6 on the PAI-1 promoter activity of our three constructs and showed that the T4G variant was less affected by IL-1β than the other variants. These findings indicate that the T4G variant may be a novel risk factor for thrombotic events.

Journal of Clinical Medicine Research, 2010

Emerging data seem to be available also on the role of active thromboprophylaxis with heparin and... more Emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). First studies which focused on the association between thrombophilia and RPL underlined the role of reduced clotting inhibitors and RPL, and subsequent studies underlined a pathogenetic role of gene variant associated to hypercoagulable state in the occurrence of RPL. On the other hand, acquired thrombophilic abnormalities as antiphipsholipid syndrome are a well known cause of RPL and should be considered for a screening. These data are relevant because recent studies suggested a role of an extensive thromprophilaxis in women with RPL that should be addressed only in case of known thrombophilia and high risk of venous thromboembolism.

International Journal of Sports Medicine, 2007

The role of renin-angiotensin system (RAS) genes, namely angiotensin-converting enzyme (ACE), ang... more The role of renin-angiotensin system (RAS) genes, namely angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin-II type 1 receptor (AT1R), in cardiovascular disease (CVD) susceptibility, is controversial and results differ among the studies on this topic . ACE gene variants are associated with increased risk of hypertension [38], myocardial infarction [8] and cardiac hypertrophy after intensive physical training , and the ACE (DD) and AGT 235TT genotypes synergistically affect left ventricular mass in endurance athletes . Similarly, the AGT gene variant M235T is related to hypertension and increased risk of coronary heart disease , and the AT1R variant A1166C to essential hypertension and coronary artery vasoconstriction [2].

Journal of Translational Medicine, 2012

Digestive and Liver Disease, 2009

Background: Adverse pregnancy outcomes are more frequent in celiac than in non-celiac women. Aims... more Background: Adverse pregnancy outcomes are more frequent in celiac than in non-celiac women. Aims: To investigate a possible role of genetic prothrombotic variants in early pregnancy loss of celiac women. Methods: Thirty-nine celiac women who had experienced early pregnancy losses (at least two losses within the first 3 months of pregnancy), and 72 celiac women with a history of one or more normal pregnancies and no pregnancy loss (controls) entered the study, at the moment of diagnosis for celiac disease. A clinical history was obtained from each woman. DNA from leukocytes was tested for: factor V Leiden (mutation G1691A), factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), beta-fibrinogen (−455 G>A), PAI-1 alleles 4G/5G, factor XIII (V34L), and HPA-1 (L33P). Results: Age at diagnosis was significantly higher (p = 0.002) in the celiac women with pregnancy losses than in controls. Of the gene variants studied, the allelic frequency of 4G variant of PAI-1, and the frequency of mutant genotypes were significantly more frequent in the group of celiac women with early pregnancy loss (p = 0.00003 and 0.028, respectively). Surprisingly, the beta-fibrinogen −455 G>A genotype distribution (but not the allelic frequency of the variant allele) significantly differed between the two groups, since variant genotypes were more frequent in the control group (p = 0.009). Conclusion: The 4G variant of the PAI-I gene may predispose to miscarriage a subset of celiac women; these data should be verified on larger populations.

Clinical Chemical Laboratory Medicine, 2000

Pharmacogenetic testing for drug-metabolizing enzymes is not yet widely used in clinical practice... more Pharmacogenetic testing for drug-metabolizing enzymes is not yet widely used in clinical practice. In an attempt to facilitate the application of this procedure, we have compared two real-time PCR-based methods, the TaqMan and the LightCycler for the pharmacogenetic evaluation of CYP2C9*2/*3 polymorphisms. Both procedures are suitable for pharmacogenetic studies. The TaqMan procedure was less expensive in terms of cost per sample, but the TaqMan apparatus is more expensive than the LightCycler apparatus.

British Journal of Ophthalmology, 2006

Aims: To evaluate the complement factor H (CFH) p.402Y.H polymorphism as a risk factor in age rel... more Aims: To evaluate the complement factor H (CFH) p.402Y.H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population. Methods: 104 unrelated Italian AMD patients and 131 unrelated controls were screened for the CFH polymorphism p.402Y.H (c.1277 T.C), which has been associated with AMD. Retinography was obtained for patients and controls; the AMD diagnosis was confirmed by fluorescein angiograms. The c.1277 T.C polymorphism was genotyped with the TaqMan real time polymerase chain reaction single nucleotide polymorphism assay. Results: The frequency of c.1277C allele was higher in AMD patients than in controls (57.2% v 39.3%; p,0.001). The odds ratio (OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (CI): 1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for sporadic (OR 4.6; CI: 2.0 to 10.5) than for familial AMD (OR 2.9; CI: 1.0 to 8.4). Genotypes were not related to either age at AMD diagnosis or to AMD phenotype. However, geographic atrophy and choroidal neovascularisation were more frequent in sporadic than in familial AMD (p = 0.027). Overall, the percentage of population attributable risk for the CC genotype was 28% (95% CI:18% to 33%). Conclusion: The association between the p.402Y.H (c.1277T.C) polymorphism and AMD applies to the Italian population and the CC genotype is more frequent in sporadic than in familial AMD cases.

Cancer …, 2007

Venous thromboembolism (VTE) is a multifactorial disease that may appear as deep vein thrombosis ... more Venous thromboembolism (VTE) is a multifactorial disease that may appear as deep vein thrombosis (DVT) of the lower or upper limb and\or pulmonary embolism (PE). Venous thromboembolism is associated with several inherited and\or acquired risk factors, cancer being the most ...