Document Detail


The maternal HLA-G 1597ΔC null mutation is associated with increased risk of pre-eclampsia and reduced HLA-G expression during pregnancy in African-American women.
MedLine Citation:
PMID:  23002110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The non-classical major histocompatibility complex molecule, human leukocyte antigen (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 pre-eclampsia (PE) in African-American women. The association between maternal and fetal genotype at six HLA-G polymorphisms and risk of PE was assessed in 372 pregnancies (314 normotensive; 58 pre-eclamptic). We observed an elevated risk of PE (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 pre-eclamptic pregnancies that were delivered preterm, suggesting an association between the null allele and the severity of PE. We then replicated the association between higher maternal 1597ΔC allele frequency and increased severity of PE (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 (sHLA-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 PE in African-American women and is predictive of circulating sHLA-G levels during pregnancy.
Authors:
Dagan A Loisel; Christine Billstrand; Kathleen Murray; Kristen Patterson; Tinnakorn Chaiworapongsa; Roberto Romero; Carole Ober
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-21
Journal Detail:
Title:  Molecular human reproduction     Volume:  19     ISSN:  1460-2407     ISO Abbreviation:  Mol. Hum. Reprod.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-08-01     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  9513710     Medline TA:  Mol Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  144-52     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
African Americans*
Alleles*
Biological Markers / blood
Case-Control Studies
Female
Gene Deletion*
Gene Expression Regulation
Gene Frequency
Genetic Predisposition to Disease
HLA-G Antigens / blood,  genetics*
Humans
Infant, Newborn
Polymorphism, Genetic
Pre-Eclampsia / blood,  ethnology*,  genetics*
Pregnancy
Risk
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
F32HL095268/HL/NHLBI NIH HHS; P01HD049480/HD/NICHD NIH HHS; T32 HL007605/HL/NHLBI NIH HHS; UL1RR024999/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/HLA-G Antigens
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome ...
Next Document:  Overcoming challenges to achieving meaningful use: insights from hospitals that successfully receive...