1. Polymorphisms of Human Placental Alkaline Phosphatase Are Associated with in Vitro Fertilization Success and Recurrent Pregnancy Loss
- Author
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Sylvie Bouvier, Philippe de Mazancourt, Daniel Vaiman, Xavier Montagutelli, Etienne Mornet, Ahmed Ziyyat, Magalie Vatin, Marie Noelle Dieudonné, Jean-Christophe Gris, L. Bellazi, Catherine Serres, Paul Laissue, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Génétique fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universidad del Rosario [Bogota], We thank Drs. Eva Nouvellon and Eric Mercier for their skillful assistance, Emilie Saurel for her help in sequence analysis, and the two reviewers for their insightful comments that improved the manuscript., Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Université Montpellier 1 (UM1), and Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)
- Subjects
Reproducibility of results ,single nucleotide ,Candidate gene ,Mouse ,Genotyping Techniques ,Intron ,Cos cells ,Gene sequence ,Cohort Studies ,Mice ,MESH: Abortion, Spontaneous ,Alkaline Phosphatase ,Fertilization in Vitro ,Genetic Predisposition to Disease ,Isoenzymes ,Polymorphism, Single Nucleotide ,0302 clinical medicine ,Pregnancy ,Recurrence ,Chlorocebus aethiops ,Haplotype ,Enzyme activity ,Priority journal ,Allele ,Genetics ,0303 health sciences ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Open reading frame ,16. Peace & justice ,3. Good health ,Retrospective study ,Phenotype ,COS Cells ,Alkaline phosphatase placenta isoenzyme ,Cohort studies ,Alkaline phosphatase ,Female ,Human ,Infertility ,Genotype ,Positional cloning ,Population ,Case control study ,Genetic predisposition to disease ,Single-nucleotide polymorphism ,Major clinical study ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Biology ,GPI-Linked Proteins ,Transfection ,Article ,Pregnancy outcome ,Cercopithecus aethiops ,Pathology and Forensic Medicine ,Andrology ,Genotyping techniques ,03 medical and health sciences ,medicine ,Animals ,Humans ,Animal model ,Gpi-linked proteins ,Polymorphism ,spontaneous ,education ,Spontaneous abortion ,030304 developmental biology ,Enzyme polymorphism ,Fertilization in vitro ,Abortion ,Reproducibility of Results ,Recurrent abortion ,Nonhuman ,medicine.disease ,Single nucleotide polymorphism ,Abortion, Spontaneous ,Placental alkaline phosphatase ,Risk factor ,Controlled study ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Fertility is a quantitative, complex character governed by a considerable number of genes. Despite clinical and scientific advances, several cases of human infertility remain unexplained. In the present study, using a positional cloning approach in a mouse model of interspecific recombinant lines, a candidate gene, ALPP, encoding the placental alkaline phosphatase, was identified as being potentially involved in recurrent spontaneous abortion. We then analyzed patients for detecting putative associations between ALPP polymorphisms, in vitro fertilization failures, and miscarriages. ALPP was sequenced in 100 controls and 100 patients affected by recurrent spontaneous abortion, from the same ethnic background. The frequency of several alleles and allelic combinations were different between recurrent spontaneous abortion and control women. One polymorphism induced a coding substitution (Ile89Leu) that was associated with a decreased risk of abortion and in vitro fertilization failure. Thereafter, the population was increased by the analysis of 92 additional controls and 612 additional patients for the coding polymorphism Ile89Leu. We finally show, by functional analysis, that the 89Leu placental alkaline phosphatase has an enhanced alkaline phosphatase activity. This study suggests that ALPP genotyping could be a strong predictor of implantation success. © 2014 American Society for Investigative Pathology.
- Published
- 2014