Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia

S. Ota, H. Miyamura, Haruki Nishizawa, Hidehito Inagaki, A. Inagaki, H. Inuzuka, M. Suzuki, J. Miyazaki, T. Sekiya, Y. Udagawa, Hiroki Kurahashi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective A common haplotype M2 consisting of minor SNP alleles located in the ANXA5 gene promoter region has been described as a risk factor for various obstetric complications such as recurrent pregnancy loss, pre-eclampsia and pregnancy-related thrombophilic disorder. However, the question of whether it is the maternal or fetal genotype that contributes to the onset of these disorders remains to be resolved. Methods We analyzed ANXA5 gene variants in the blood and placental tissues from pre-eclampsia patients and normotensive controls. ANXA5 expression was examined by qRT-PCR, Western blotting and immunostaining. Results were compared between M2 and non-M2 carriers. Results The M2 haplotype was found to be significantly frequent in placentas from pre-eclamptic patients relative to the controls (25.5% versus 10%, P = 0.044), In contrast, no significant differences were observed in maternal blood (13.0% versus 11.3%, P = 0.597). The placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When examined by Western blot and immunostaining, the ANXA5 protein levels were found to be affected more by the placental than the maternal genotype. Histological examination of the placentas from the pre-eclamptic patients demonstrated that a placental M2 haplotype correlated more closely than maternal M2 with the severity of perivillous fibrin deposition. Conclusions Although preliminary, these results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter, whether transmitted maternally or paternally, might be an essential determinant of an increased risk of pre-eclampsia via local thrombophilia at the feto-maternal interface.

Original languageEnglish
Pages (from-to)1202-1210
Number of pages9
JournalPlacenta
Volume34
Issue number12
DOIs
Publication statusPublished - 01-12-2013

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Pre-Eclampsia
Mothers
Haplotypes
Genes
Placenta
Western Blotting
Alleles
Genotype
Pregnancy
Thrombophilia
Fibrin
Genetic Promoter Regions
Obstetrics
Single Nucleotide Polymorphism
Polymerase Chain Reaction
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology
  • Developmental Biology

Cite this

Ota, S. ; Miyamura, H. ; Nishizawa, Haruki ; Inagaki, Hidehito ; Inagaki, A. ; Inuzuka, H. ; Suzuki, M. ; Miyazaki, J. ; Sekiya, T. ; Udagawa, Y. ; Kurahashi, Hiroki. / Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia. In: Placenta. 2013 ; Vol. 34, No. 12. pp. 1202-1210.
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abstract = "Objective A common haplotype M2 consisting of minor SNP alleles located in the ANXA5 gene promoter region has been described as a risk factor for various obstetric complications such as recurrent pregnancy loss, pre-eclampsia and pregnancy-related thrombophilic disorder. However, the question of whether it is the maternal or fetal genotype that contributes to the onset of these disorders remains to be resolved. Methods We analyzed ANXA5 gene variants in the blood and placental tissues from pre-eclampsia patients and normotensive controls. ANXA5 expression was examined by qRT-PCR, Western blotting and immunostaining. Results were compared between M2 and non-M2 carriers. Results The M2 haplotype was found to be significantly frequent in placentas from pre-eclamptic patients relative to the controls (25.5{\%} versus 10{\%}, P = 0.044), In contrast, no significant differences were observed in maternal blood (13.0{\%} versus 11.3{\%}, P = 0.597). The placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When examined by Western blot and immunostaining, the ANXA5 protein levels were found to be affected more by the placental than the maternal genotype. Histological examination of the placentas from the pre-eclamptic patients demonstrated that a placental M2 haplotype correlated more closely than maternal M2 with the severity of perivillous fibrin deposition. Conclusions Although preliminary, these results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter, whether transmitted maternally or paternally, might be an essential determinant of an increased risk of pre-eclampsia via local thrombophilia at the feto-maternal interface.",
author = "S. Ota and H. Miyamura and Haruki Nishizawa and Hidehito Inagaki and A. Inagaki and H. Inuzuka and M. Suzuki and J. Miyazaki and T. Sekiya and Y. Udagawa and Hiroki Kurahashi",
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Ota, S, Miyamura, H, Nishizawa, H, Inagaki, H, Inagaki, A, Inuzuka, H, Suzuki, M, Miyazaki, J, Sekiya, T, Udagawa, Y & Kurahashi, H 2013, 'Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia', Placenta, vol. 34, no. 12, pp. 1202-1210. https://doi.org/10.1016/j.placenta.2013.09.010

Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia. / Ota, S.; Miyamura, H.; Nishizawa, Haruki; Inagaki, Hidehito; Inagaki, A.; Inuzuka, H.; Suzuki, M.; Miyazaki, J.; Sekiya, T.; Udagawa, Y.; Kurahashi, Hiroki.

In: Placenta, Vol. 34, No. 12, 01.12.2013, p. 1202-1210.

Research output: Contribution to journalArticle

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T1 - Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia

AU - Ota, S.

AU - Miyamura, H.

AU - Nishizawa, Haruki

AU - Inagaki, Hidehito

AU - Inagaki, A.

AU - Inuzuka, H.

AU - Suzuki, M.

AU - Miyazaki, J.

AU - Sekiya, T.

AU - Udagawa, Y.

AU - Kurahashi, Hiroki

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Objective A common haplotype M2 consisting of minor SNP alleles located in the ANXA5 gene promoter region has been described as a risk factor for various obstetric complications such as recurrent pregnancy loss, pre-eclampsia and pregnancy-related thrombophilic disorder. However, the question of whether it is the maternal or fetal genotype that contributes to the onset of these disorders remains to be resolved. Methods We analyzed ANXA5 gene variants in the blood and placental tissues from pre-eclampsia patients and normotensive controls. ANXA5 expression was examined by qRT-PCR, Western blotting and immunostaining. Results were compared between M2 and non-M2 carriers. Results The M2 haplotype was found to be significantly frequent in placentas from pre-eclamptic patients relative to the controls (25.5% versus 10%, P = 0.044), In contrast, no significant differences were observed in maternal blood (13.0% versus 11.3%, P = 0.597). The placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When examined by Western blot and immunostaining, the ANXA5 protein levels were found to be affected more by the placental than the maternal genotype. Histological examination of the placentas from the pre-eclamptic patients demonstrated that a placental M2 haplotype correlated more closely than maternal M2 with the severity of perivillous fibrin deposition. Conclusions Although preliminary, these results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter, whether transmitted maternally or paternally, might be an essential determinant of an increased risk of pre-eclampsia via local thrombophilia at the feto-maternal interface.

AB - Objective A common haplotype M2 consisting of minor SNP alleles located in the ANXA5 gene promoter region has been described as a risk factor for various obstetric complications such as recurrent pregnancy loss, pre-eclampsia and pregnancy-related thrombophilic disorder. However, the question of whether it is the maternal or fetal genotype that contributes to the onset of these disorders remains to be resolved. Methods We analyzed ANXA5 gene variants in the blood and placental tissues from pre-eclampsia patients and normotensive controls. ANXA5 expression was examined by qRT-PCR, Western blotting and immunostaining. Results were compared between M2 and non-M2 carriers. Results The M2 haplotype was found to be significantly frequent in placentas from pre-eclamptic patients relative to the controls (25.5% versus 10%, P = 0.044), In contrast, no significant differences were observed in maternal blood (13.0% versus 11.3%, P = 0.597). The placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When examined by Western blot and immunostaining, the ANXA5 protein levels were found to be affected more by the placental than the maternal genotype. Histological examination of the placentas from the pre-eclamptic patients demonstrated that a placental M2 haplotype correlated more closely than maternal M2 with the severity of perivillous fibrin deposition. Conclusions Although preliminary, these results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter, whether transmitted maternally or paternally, might be an essential determinant of an increased risk of pre-eclampsia via local thrombophilia at the feto-maternal interface.

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