The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations

Matthew P. Johnson, Linda T. Roten, Thomas D. Dyer, Christine E. East, Siri Forsmo, John Blangero, Shaun P. Brennecke, Rigmor Austgulen, Eric K. Moses

Research output: Contribution to journalArticle

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Abstract

Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs3734016, Puncorr = 0.009) and for the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782, Puncorr = 0.004). In the Norwegian cohort we identified evidence of a genetic association for ERAP1 (rs34750, Puncorr = 0.011) and for ERAP2 (rs17408150, P uncorr = 0.009). The ERAP2 SNPs in both cohorts remained statistically significant (rs2549782, Pcorr = 0.018; rs17408150, Pcorr = 0.039) after corrections at an experiment-wide level. The ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood pressure regulation and essential hypertension in addition to innate immune and inflammatory responses. Perturbations within vascular, immunological and inflammatory pathways constitute important physiological mechanisms in preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder.

Original languageEnglish (US)
Pages (from-to)655-666
Number of pages12
JournalHuman Genetics
Volume126
Issue number5
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Aminopeptidases
Pre-Eclampsia
Endoplasmic Reticulum
Population
Genes
New Zealand
Genetic Linkage
Single Nucleotide Polymorphism
Pregnancy
Computational Biology
Proteinuria
Innate Immunity
Blood Vessels
Chromosomes
Blood Pressure
Hypertension
Enzymes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Johnson, M. P., Roten, L. T., Dyer, T. D., East, C. E., Forsmo, S., Blangero, J., ... Moses, E. K. (2009). The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Human Genetics, 126(5), 655-666. https://doi.org/10.1007/s00439-009-0714-x

The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. / Johnson, Matthew P.; Roten, Linda T.; Dyer, Thomas D.; East, Christine E.; Forsmo, Siri; Blangero, John; Brennecke, Shaun P.; Austgulen, Rigmor; Moses, Eric K.

In: Human Genetics, Vol. 126, No. 5, 2009, p. 655-666.

Research output: Contribution to journalArticle

Johnson, MP, Roten, LT, Dyer, TD, East, CE, Forsmo, S, Blangero, J, Brennecke, SP, Austgulen, R & Moses, EK 2009, 'The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations', Human Genetics, vol. 126, no. 5, pp. 655-666. https://doi.org/10.1007/s00439-009-0714-x
Johnson, Matthew P. ; Roten, Linda T. ; Dyer, Thomas D. ; East, Christine E. ; Forsmo, Siri ; Blangero, John ; Brennecke, Shaun P. ; Austgulen, Rigmor ; Moses, Eric K. / The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. In: Human Genetics. 2009 ; Vol. 126, No. 5. pp. 655-666.
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AU - Roten, Linda T.

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AU - Blangero, John

AU - Brennecke, Shaun P.

AU - Austgulen, Rigmor

AU - Moses, Eric K.

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