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A novel ERAP2 haplotype structure in a chilean population: Implications for ERAP2 protein expression and preeclampsia risk
Indexado
Scopus SCOPUS_ID:84915771682
DOI 10.1002/MGG3.13
Año 2013
Tipo

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


Abstract



Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase2 (ERAP2) gene are associated with preeclampsia (PE) in different populations. rs2549782, a coding variant (N392K) that significantly affects substrate specificity, is in linkage disequilibrium (LD) with rs2248374, a marker SNP associated with ERAP2 protein expression in previously studied populations. As a result of nonsense-mediated RNA decay, ERAP2 protein is not expressed from the rs2248374 G allele. We previously reported that the fetalrs2549782 minor G allele is associated with PE in African-Americans, but not in Chileans. In this study, we found that rs2549782 was in LD with rs2248374in African-Americans, but not in Chileans. The unexpected lack of strong LD in Chileans raised the possibility that rs2248374 could be associated with PE in the absence of an association with rs2549782. However, we found no significant association for this allele with PE in Chileans. Chileans homozygous for thers2248374 G allele did not express 110 kDa ERAP2 protein, consistent with nonsense-mediated RNA decay, and carriers of the rs2248374 A allele did. We conclude that the Chilean ERAP2 haplotype structure allows for the expression of the major T allele of rs2549782 encoding 392N, which could impact peptide trimming and antigen presentation. Our discovery of racial differences in genetic structure and association with PE reveal heretofore unrecognized complexity of the ERAP2 locus

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Disciplinas de Investigación



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Genetics & Heredity
Scopus
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SciELO
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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

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Autores - Afiliación



Ord. Autor Género Institución - País
1 Vanhille, Derek L. Hombre VCU School of Medicine - Estados Unidos
2 Hill, Lori D. Mujer VCU School of Medicine - Estados Unidos
3 Hilliard, Dashaunda D. - VCU School of Medicine - Estados Unidos
4 Lee, Eun D. Mujer VCU School of Medicine - Estados Unidos
5 Teves, Maria E. Mujer VCU School of Medicine - Estados Unidos
6 Srinivas, Sindhu - University of Pennsylvania Perelman School of Medicine - Estados Unidos
7 KUSANOVIC-PIVCEVIC, JUAN PEDRO Hombre National Institute of Child Health and Human Development - Estados Unidos
Hospital Dr Sotero del Rio - Chile
Pontificia Universidad Católica de Chile - Chile
National Institute of Child Health and Human Development (NICHD) - Estados Unidos
8 GOMEZ-MORA, RICARDO ALEJANDRO Hombre Hospital Dr Sotero del Rio - Chile
Pontificia Universidad Católica de Chile - Chile
9 Stratikos, Efstratios Hombre Demokritos National Centre for Scientific Research - Grecia
National Centre for Scientific Research "DEMOKRITOS" - Grecia
10 Aelovitz, Michal Hombre University of Pennsylvania Perelman School of Medicine - Estados Unidos
11 Romero, Roberto Hombre National Institute of Child Health and Human Development - Estados Unidos
National Institute of Child Health and Human Development (NICHD) - Estados Unidos
12 STRAUSS, JEROME F., III Hombre VCU School of Medicine - Estados Unidos

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Financiamiento



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