Publications (56) View all
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Article: Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews.
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ABSTRACT: BACKGROUND: Factor XI (FXI) deficiency is one of the most frequent inherited disorders in Ashkenazi Jews. Two predominant founder mutations termed type II (p.Glu117Stop) and type III (p.Phe283Leu) account for most cases. OBJECTIVES: To present clinical aspects of a third FXI mutation, type I (c.1716+1G>A), which is also prevalent in Ashkenazi Jews and to discern a possible founder effect. PATIENTS/METHODS: Bleeding manifestations, FXI levels and origin of members of 13 unrelated families harboring the type I mutation were determined. In addition, eight intragenic and five extragenic polymorphisms were analysed in patients with type I mutation, in 16 unrelated type II homozygotes, in 23 unrelated type III homozygotes and in Ashkenazi Jewish controls. Analysis of these polymorphisms enabled haplotype analysis and estimation of the age of the type I mutation. RESULTS: Four of 16 type I heterozygotes (25%) and 6 of 12 (50%) compound heterozygotes for type I mutation (I/II and I/III), or a type I homozygote had bleeding manifestations. Haplotype analysis disclosed that like type II and type III mutations, the type I is also an ancestral mutation. An age estimate revealed that the type I mutation occurred approximately 600 years ago. The geographic distribution of affected families suggested that there was a distinct origin of the type I mutation in Eastern Europe. CONCLUSIONS: The rather rare type I mutation in the FXI gene is a third founder mutation in Ashkenazi Jews. © 2013 International Society on Thrombosis and Haemostasis.Journal of Thrombosis and Haemostasis 01/2013; · 5.73 Impact Factor -
Article: Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation.
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ABSTRACT: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutations suffer from increased rates of liver fibrosis. We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fibrosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. Fifty two of the patients were categorized as "fast fibrosers" and 116 as "slow fibrosers"; 13% of the "fast fibrosers" carried the PT20210 mutation as compared with 5.5% of the "slow fibrosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fibrosis. Carriage of the PT20210 mutation is related to an increased rate of liver fibrosis in HCV patients.World Journal of Gastroenterology 12/2011; 17(45):5007-13. · 2.47 Impact Factor -
Article: Melatonin and mental capacities in newborn infants.
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ABSTRACT: To investigate the role of melatonin in the emergence of mental capacities in the newborn infant. Assessment of Preterm Infant Behavior examination was performed at 2 weeks post-term age for 39 (21 preterm and 18 term) infants. 6-Suphatoxymelatonin from nocturnal urine samples was analyzed by enzyme-linked immunosorbent assays, and the Mental Developmental Index, assessed by Bayley scales, was correlated at 4, 6, and 9 months' corrected age. Multivariate analysis of variance with repeated measures showed that improved autonomic function at 2 weeks of age was associated with higher Mental Developmental Index scores at 9 months when related to the amount of melatonin at 4, 6, and 9 months of age. Early compromised autonomic system function in preterm infants is associated with lower mental capacities and is related to lower melatonin levels at later ages.The Journal of pediatrics 02/2011; 159(1):99-103.e1. · 4.02 Impact Factor -
Article: Association of the -757T>C polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis.
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ABSTRACT: C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of atherosclerosis. CRP gene single nucleotide polymorphisms (SNPs) have been shown to be associated with CRP concentration; however, their independent effect on atherosclerosis has not been yet established. We aimed to determine whether the 5'-flanking -757T>C CRP gene polymorphism is associated with CRP concentration and carotid atherosclerosis. We genotyped the -757T>C CRP gene SNP and determined the concentration of serum CRP, the intima-media thickness (IMT) of the common carotid artery and the existence of plaque/s in 612 apparently healthy men and women aged 66+/-10 years. Carriers of the CRP -757C allele presented with higher IMT and higher CRP concentrations (p=0.002, p=0.042, respectively). After adjustment for vascular risk factors, linear regression analysis showed an independent effect of CRP -757C allele on carotid IMT, beyond serum CRP concentrations. This SNP was also associated with carotid plaque occurrence (O.R. 1.74, 95% CI 1.1-2.77, p=0.002). The present study provides evidence that a genetic variant of CRP gene is associated with carotid atherosclerosis, independently of traditional vascular risk factors. Further large-scale genomic studies are required, which may identify the genetic vulnerable subjects to develop atherosclerosis.Thrombosis Research 06/2009; 124(4):458-62. · 2.44 Impact Factor -
Article: Glycohaemoglobin as a determinant of increased fibrinogen concentrations and low-grade inflammation in apparently healthy nondiabetic individuals.
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ABSTRACT: To determine the potential role of glycohaemoglobin as a possible determinant of increased fibrinogen concentrations and low-grade inflammation in a group of apparently healthy, nondiabetic individuals not expressing clinically overt atherothrombosis. We performed a cross-sectional analysis of the concentrations of glycohaemoglobin alongside the concentrations of quantitative fibrinogen and high-sensitivity C-reactive protein (hs-CRP). In all, 1511 males and 757 apparently healthy females, without diabetes mellitus or clinically evident atherothrombotic disease, were enrolled in the study during their routine annual health check-up. Glycohaemoglobin entered the linear regression models as a significant determinant of quantitative fibrinogen in both genders and of hs-CRP in men. We found this to be true even following the inclusion of multiple variables known to influence the intensity of low-grade inflammation, such as age, gender, waist circumference, body mass index, blood pressure, medications, hormone therapy, glucose levels (normal or impaired fasting glucose), smoking habits, family history of coronary artery disease, lipid profile as well as alcohol consumption and sports intensity. We found glycohaemoglobin to be a significant determinant of fibrinogen concentrations in apparently healthy nondiabetic individuals not yet presenting with evident atherothrombosis. This observation supports the idea that glycohaemoglobin might have an effect on fibrinogen concentrations in both genders and on hs-CRP in men. Moreover, our results suggest that glycohaemoglobin should be perceived as a continuous variable without a 'normal' cut-off point, as it may exhibit a detrimental role even when present in relatively low levels.Clinical Endocrinology 03/2008; 68(2):182-9. · 3.17 Impact Factor
