| Methylation allelic polymorphism (MAP) in chorionic gonadotropin beta5 (CGB5) and its association with pregnancy success. | |
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MedLine Citation:
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PMID: 20962020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Increased epigenetic variability in the placenta may have evolved in response to its role in mediating the conflicting demands of the mother and fetus. One essential guardian of early pregnancy maintenance is the placental hormone human chorionic gonadotropin (HCG). OBJECTIVE: Among the four primate-specific duplicate HCGβ-coding genes, chorionic gonadotropin-β8 (CGB8) and chorionic gonadotropin-β5 (CGB5) jointly contribute 62-82% of the total HCGβ transcript pool. Because these genes share common features with known imprinted placenta-expressed loci, we addressed the role of epigenetic mechanisms affecting their action. DESIGN AND SUBJECTS: Parental origin of CGB5 and CGB8 transcripts and promoter methylation patterns were addressed in trophoblastic tissues from 23 mother-offspring duos and nine mother-father-offspring trios including the following: 1) third-trimester normal delivery at term (n = 14), 2) first-trimester elective termination of uncomplicated pregnancy (n = 10), and 3) first-trimester recurrent (≥3) miscarriage (n = 8). RESULTS: A normal uncomplicated pregnancy was characterized by balanced, biallelic expression of CGB5 and CGB8. However, in three (two recurrent miscarriage and one early elective termination of uncomplicated pregnancy) of nine genetically informative cases of CGB5, monoallelic expression of maternal alleles and hemimethylated gene promoters were identified. CONCLUSION: Our finding may represent a novel methylation allelic polymorphism or gain of imprinting in CGB5 promoter leading to expressional silencing of paternal alleles and increasing susceptibility to pregnancy loss. Aberrant methylation patterns in placenta may result from random reprogramming defects affecting normal implantation process. Alternatively, methylation allelic polymorphism in the placenta favoring the failure of pregnancy may arise as a response to cellular stress caused by, in general, aneuploidy or conditions in placental-maternal interface. |
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Authors:
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Liis Uusküla; Kristiina Rull; Liina Nagirnaja; Maris Laan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-20 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 96 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-06 Completed Date: 2011-02-04 Revised Date: 2011-07-26 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E199-207 Citation Subset: AIM; IM |
Affiliation:
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Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Chorionic Gonadotropin, beta Subunit, Human / genetics*, metabolism DNA Methylation / genetics* Female Genomic Imprinting Humans Placenta / metabolism* Polymorphism, Genetic* Pregnancy Pregnancy Outcome Pregnancy Trimester, First / genetics Reverse Transcriptase Polymerase Chain Reaction Trophoblasts / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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070191/Z/03/Z//Wellcome Trust; 55005617//Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Chorionic Gonadotropin, beta Subunit, Human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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