| Variation in the HLA-G promoter region influences miscarriage rates. | |
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MedLine Citation:
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PMID: 12721954 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The HLA-G gene is primarily expressed in placental cells that invade the maternal decidua during pregnancy. This gene encodes multiple isoforms that fulfill a variety of functions at the maternal-fetal interface throughout gestation. Recently, a null allele for the most abundant HLA-G isoform was associated with recurrent miscarriage in two independent studies, suggesting that reduced levels of the HLA-G1 protein may compromise successful pregnancy. We initiated the present study to determine whether other polymorphisms that could affect expression levels of HLA-G were associated with fetal loss in women participating in a 15-year prospective study of pregnancy outcome. We genotyped these subjects for 18 single-nucleotide polymorphisms in the 1,300 bp upstream of exon 1, 13 of which were identified as part of this study, as well as for an insertion/deletion (in/del) polymorphism in the 3' untranslated region. The 18 SNPs defined eight unique haplotypes. One polymorphism, -725C/G, was associated with fetal loss, with an increased risk for miscarriage in couples in which both partners carried the -725G allele, compared with couples not carrying this allele (odds ratio 2.76, 95% confidence interval 1.08-7.09; P=.035). Further, the G at nucleotide -725 creates a CpG dinucleotide, and we demonstrate that this CpG site is methylated on -725G alleles. Overall, this study identified extraordinary levels of variation in the 5'-upstream regulatory region of HLA-G and provides evidence for an association between a promoter-region SNP and fetal loss rates, further attesting to the novel features and critical role of this gene in pregnancy. |
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Authors:
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Carole Ober; Carrie L Aldrich; Inna Chervoneva; Christine Billstrand; Fedik Rahimov; Heather L Gray; Terry Hyslop |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-04-29 |
Journal Detail:
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Title: American journal of human genetics Volume: 72 ISSN: 0002-9297 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-05-15 Completed Date: 2003-07-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 1425-35 Citation Subset: IM |
Affiliation:
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Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA. c-ober@genetics.uchicago.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Abortion, Spontaneous
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genetics* Alleles Female Gene Frequency Genetic Variation* Genotype HLA Antigens / genetics* Haplotypes Histocompatibility Antigens Class I / genetics* Humans Mutation Polymorphism, Single Nucleotide Pregnancy Promoter Regions, Genetic* Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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HD21244/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HLA Antigens; 0/HLA-G antigen; 0/Histocompatibility Antigens Class I |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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