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      Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran

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          Abstract

          Background:

          Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D).

          Objective:

          In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran.

          Materials and Methods:

          Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χ 2 and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression.

          Results:

          There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL.

          Conclusion:

          ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion.

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          Most cited references38

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          ACE polymorphisms.

          Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.
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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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              The functional role of the renin-angiotensin system in pregnancy and preeclampsia.

              During normal pregnancy, the renin-angiotensin system (RAS) plays a vitally important role in salt balance and subsequent well-being of mother and fetus. In this balance, one must consider not only the classical renal RAS but also that of the uteroplacental unit, where both maternal and fetal tissues contribute to the signaling cascade. Many studies have shown that in normal pregnancy there is an increase in almost all of the components of the RAS. In derangements of pregnancy this delicate equilibrium can become unbalanced. Preeclampsia is one such case. It is a disorder of pregnancy characterized by hypertension, proteinuria and placental abnormalities associated with shallow trophoblast invasion and impaired spiral artery remodeling. Despite being a leading cause of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Immunological mechanisms and the RAS have been long considered to be involved in the development of preeclampsia. Numerous recent studies demonstrate the presence of the angiotensin II type I receptor agonistic autoantibody (AT1-AA). This autoantibody can induce many key features of the disorder and upregulate molecules involved in the pathogenesis of preeclampsia. Here we review the functional role of the RAS during pregnancy and the impact of AT1-AA on preeclampsia.
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                Author and article information

                Journal
                Int J Reprod Biomed (Yazd)
                Int J Reprod Biomed (Yazd)
                IJRB
                International Journal of Reproductive Biomedicine
                Research and Clinical Center for Infertility (Yazd, Iran )
                2476-4108
                2476-3772
                May 2016
                : 14
                : 5
                : 323-328
                Affiliations
                [1 ] Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
                [2 ] Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
                [3 ] Immunogenetic Research center, Molecular and cell Biology Research Centre, Mazandaran University of Medical Sciences, Sari, Iran.
                Author notes
                Corresponding Author: Seyed Mohammad Bagher Hashemi-Soteh: Department of Genetics, School of Medicine, Mazandaran University of Medical Sciences, Farahabad Road., Sari, Iran. P.O. Box. 481751665 ,Email: hashemisoteh@gmail.com, Tel: (+98) 9111164034
                Article
                ijrb-14-323
                4910031
                27326417
                c26d2f2e-23be-4d8d-a714-d53cb7109736

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 September 2015
                : 17 February 2016
                Categories
                Original Article

                angiotensin converting enzyme,platelet glycoprotein iiia,recurrent abortion

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