| The maternal HLA-G 1597{Delta}C null mutation is associated with increased risk of preeclampsia and reduced HLA-G expression during pregnancy in African American women. | |
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MedLine Citation:
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PMID: 23002110 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The non-classical MHC molecule, HLA-G, is thought to contribute to maternal immune tolerance and successful placentation during pregnancy. Genetic polymorphisms in HLA-G are known to influence expression levels as well as the relative expression of individual protein isoforms. As diminished or aberrant HLA-G expression patterns may contribute to the development of certain pregnancy complications, we sought to investigate the association between functional HLA-G polymorphisms and the risk of preeclampsia in African American women. The association between maternal and fetal genotype at six HLA-G polymorphisms and risk of preeclampsia was assessed in 372 pregnancies (314 normotensive; 58 preeclamptic). We observed an elevated risk of preeclampsia (P=0.00027) in pregnancies where the mother carried the 1597ΔC allele, a null allele that abolishes expression of full-length HLA-G isoforms. Furthermore, the frequency of the maternal 1597ΔC allele was highest in the subset of preeclamptic pregnancies that were delivered preterm, suggesting an association between the null allele and the severity of preeclampsia. We then replicated the association between higher maternal 1597ΔC allele frequency and increased severity of preeclampsia (P=0.038) in an independent sample of 533 African American women. Finally, to investigate the mechanistic basis of this association, we measured circulating soluble HLA-G concentrations in maternal serum collected during pregnancy in 51 healthy, normotensive African American control women and found significantly lower levels in women carrying the 1597ΔC allele (P=0.012). These results demonstrate that maternal HLA-G genotype is significantly associated with risk of preeclampsia in African American women and is predictive of circulating sHLA-G levels during pregnancy. |
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Authors:
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Dagan A Loisel; Christine Billstrand; Kathleen Murray; Kristen Patterson; Tinnakorn Chaiworaphongsa; Roberto Romero; Carole Ober |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-21 |
Journal Detail:
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Title: Molecular human reproduction Volume: - ISSN: 1460-2407 ISO Abbreviation: Mol. Hum. Reprod. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9513710 Medline TA: Mol Hum Reprod Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Human Genetics. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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