Polymorphisms of Human Placental Alkaline Phosphatase Are Associated with in Vitro Fertilization Success and Recurrent Pregnancy Loss
Copyright policy )Polymorphisms of Human Placental Alkaline Phosphatase Are Associated with in Vitro Fertilization Success and Recurrent Pregnancy Loss
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.
- UNIVERSITE PARIS DESCARTES France
- University Hospital of Montpellier France
- University of Paris France
- University of Nîmes France
- Versailles Saint-Quentin-en-Yvelines University France
Reproducibility of results, single nucleotide, Mouse, Genotyping Techniques, Intron, Cos cells, Gene sequence, Cohort Studies, Mice, Pregnancy, Recurrence, Chlorocebus aethiops, Haplotype, Enzyme activity, Priority journal, Allele, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Single Nucleotide, Open reading frame, [SDV] Life Sciences [q-bio], Isoenzymes, Retrospective study, Phenotype, COS Cells, Alkaline phosphatase placenta isoenzyme, Cohort studies, Female, MESH: Abortion, Human, Genotype, Case control study, 610, Genetic predisposition to disease, Major clinical study, Fertilization in Vitro, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, GPI-Linked Proteins, Transfection, Polymorphism, Single Nucleotide, Article, Pregnancy outcome, Cercopithecus aethiops, Genotyping techniques, Alkaline phosphatase, Animals, Humans, Animal model, Gpi-linked proteins, Genetic Predisposition to Disease, Polymorphism, spontaneous, Spontaneous abortion, Enzyme polymorphism, Fertilization in vitro, Spontaneous, Abortion, Reproducibility of Results, Recurrent abortion, Nonhuman, Alkaline Phosphatase, Single nucleotide polymorphism, Abortion, Spontaneous, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Risk factor, Controlled study, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Reproducibility of results, single nucleotide, Mouse, Genotyping Techniques, Intron, Cos cells, Gene sequence, Cohort Studies, Mice, Pregnancy, Recurrence, Chlorocebus aethiops, Haplotype, Enzyme activity, Priority journal, Allele, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Single Nucleotide, Open reading frame, [SDV] Life Sciences [q-bio], Isoenzymes, Retrospective study, Phenotype, COS Cells, Alkaline phosphatase placenta isoenzyme, Cohort studies, Female, MESH: Abortion, Human, Genotype, Case control study, 610, Genetic predisposition to disease, Major clinical study, Fertilization in Vitro, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, GPI-Linked Proteins, Transfection, Polymorphism, Single Nucleotide, Article, Pregnancy outcome, Cercopithecus aethiops, Genotyping techniques, Alkaline phosphatase, Animals, Humans, Animal model, Gpi-linked proteins, Genetic Predisposition to Disease, Polymorphism, spontaneous, Spontaneous abortion, Enzyme polymorphism, Fertilization in vitro, Spontaneous, Abortion, Reproducibility of Results, Recurrent abortion, Nonhuman, Alkaline Phosphatase, Single nucleotide polymorphism, Abortion, Spontaneous, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Risk factor, Controlled study, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
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