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      Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients

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          Abstract

          Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases) and 206 healthy multiparous women (controls) in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs) markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population.

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          Thrombophilic disorders and fetal loss: a meta-analysis.

          Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and non-recurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. We included 31 studies. Factor V Leiden was associated with early (OR 2.01, 95% CI 1.13-3.58) and late (7.83, 2.83-21.67) recurrent fetal loss, and late non-recurrent fetal loss (3.26, 1.82-5.83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3.48, 1.58-7.69), and prothrombin G20210A mutation with early recurrent (2.56, 1.04-.29) and late non-recurrent (2.30, 1.09-4.87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14.72, 0.99-218.01) and late non-recurrent fetal loss (7.39, 1.28-42.63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.
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            Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate.

            Although it is well established that Hispanics generally have a mixed Native American, African, and European ancestry, the dynamics of admixture at the foundation of Hispanic populations is heterogeneous and poorly documented. Genetic analyses are potentially very informative for probing the early demographic history of these populations. Here we evaluate the genetic structure and admixture dynamics of a province in northwest Colombia (Antioquia), which prior analyses indicate was founded mostly by Spanish men and native women. We examined surname, Y chromosome, and mtDNA diversity in a geographically structured sample of the region and obtained admixture estimates with highly informative autosomal and X chromosome markers. We found evidence of reduced surname diversity and support for the introduction of several common surnames by single founders, consistent with the isolation of Antioquia after the colonial period. Y chromosome and mtDNA data indicate little population substructure among founder Antioquian municipalities. Interestingly, despite a nearly complete Native American mtDNA background, Antioquia has a markedly predominant European ancestry at the autosomal and X chromosome level, which suggests that, after foundation, continuing admixture with Spanish men (but not with native women) increased the European nuclear ancestry of Antioquia. This scenario is consistent with historical information and with results from population genetics theory.
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              Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening.

              To estimate ethnic-specific prevalence rates of factor V Leiden, an inherited defect of hemostasis associated with risk of venous thrombosis. Survey of 4047 American men and women participating in the Physicians' Health Study (PHS) or in the Women's Health Study (WHS). All study participants were free of myocardial infarction, stroke, or venous thrombosis. Prevalence of G1691A Leiden mutation in the gene coding for coagulation factor V was determined in the PHS group using polymerase chain reaction techniques and, in the WHS group, a second-generation activated protein C (APC)-resistance screening test with genetic confirmation of all borderline and low-value results. In 2468 Caucasian Americans, carrier frequency of factor V Leiden was 5.27% (95% confidence interval [CI], 4.42%-6.22%). Carrier frequency was 2.21% in 407 Hispanic Americans, 1.23% in 650 African Americans, 0.45% in 442 Asian Americans, and 1.25% in 80 Native Americans. Thus, prevalence of factor V Leiden was less among minority subjects (P=.001). Carrier frequencies were similar in Caucasian men and women (5.53% vs 4.85% respectively, P=.5). These data indicate that prevalence of factor V Leiden is greater among Caucasians than minority Americans. These data have implications for clinicians considering whether to screen for factor V Leiden in high-risk groups such as those with prior venous thromboses or coexistent defects of anticoagulation and women at risk for postpartum thrombosis or seeking oral contraceptives.
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                Author and article information

                Journal
                Thrombosis
                Thrombosis
                THROMB
                Thrombosis
                Hindawi Publishing Corporation
                2090-1488
                2090-1496
                2012
                11 April 2012
                : 2012
                : 367823
                Affiliations
                1Grupo Reproducción, Universidad de Antioquia, Medellín, Colombia
                2Grupo de Estudio en Trombosis, Universidad de Antioquia, Medellín, Colombia
                3Departamento de Ginecología y Obstetricia, Universidad de Antioquia and Hospital Universitario San Vicente de Paúl, Medellín, Colombia
                4GENMOL, Universidad de Antioquia, Medellín, Colombia
                Author notes

                Academic Editor: Solaf Elsayed

                Article
                10.1155/2012/367823
                3345256
                22577540
                e8782ed7-b55f-432d-8d7d-2258d4bd0cd3
                Copyright © 2012 Henry Cardona et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 November 2011
                : 27 January 2012
                Categories
                Research Article

                Hematology
                Hematology

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