title: Polymorphisms of human placental alkaline phosphatase are associated with in vitro fertilization success and recurrent pregnancy loss.
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.
authors.affiliation: French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; French National Centre for Scientific Research (CNRS), UMR 8104, Paris, France; University of Paris V: René Descartes, Paris, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Vatin
authors.affiliation: Department of Haematology, University Hospital, and EA2992, University of Montpellier 1, Nîmes, France; Laboratory of Haematology, Faculty of Pharmaceutical and Biological Sciences, University of Montpellier 1, Montpellier, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bouvier
authors.affiliation: Cellular and Genetic Pathology Unit, EA 2493, Faculty of Health Sciences, Paris-Ile de France Ouest, University of Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Bellazi
authors.affiliation: Department of Functional Mouse Genetics, Institut Pasteur, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.affiliation: Genetics Unit, School of Medicine and Health Sciences, University of Rosario, Bogotá, Colombia; Department of Functional Genomics and Molecular Genetics, VITA, Center of Reproduction Assistance, Bogotá, Colombia.
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
authors.affiliation: French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; French National Centre for Scientific Research (CNRS), UMR 8104, Paris, France; University of Paris V: René Descartes, Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ziyyat
authors.affiliation: French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; French National Centre for Scientific Research (CNRS), UMR 8104, Paris, France; University of Paris V: René Descartes, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Serres
authors.affiliation: Cellular and Genetic Pathology Unit, EA 2493, Faculty of Health Sciences, Paris-Ile de France Ouest, University of Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Mazancourt
authors.affiliation: Cellular and Genetic Pathology Unit, EA 2493, Faculty of Health Sciences, Paris-Ile de France Ouest, University of Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Dieudonné
authors.affiliation: Cellular and Genetic Pathology Unit, EA 2493, Faculty of Health Sciences, Paris-Ile de France Ouest, University of Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Mornet
authors.affiliation: French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; French National Centre for Scientific Research (CNRS), UMR 8104, Paris, France; University of Paris V: René Descartes, Paris, France. Electronic address: daniel.vaiman@inserm.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.affiliation: Department of Haematology, University Hospital, and EA2992, University of Montpellier 1, Nîmes, France; Laboratory of Haematology, Faculty of Pharmaceutical and Biological Sciences, University of Montpellier 1, Montpellier, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Gris
mesh_terms: D000022:Abortion, Spontaneous / Q000201:enzymology* / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D012008:Recurrence; D015203:Reproducibility of Results; D014162:Transfection
chemical_list: D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental