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Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia
BACKGROUND: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this assoc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Avicenna Research Institute
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648866/ https://www.ncbi.nlm.nih.gov/pubmed/33209740 http://dx.doi.org/10.18502/jri.v21i4.4328 |
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author | Ohwaki, Akiko Nishizawa, Haruki Kato, Asuka Kato, Takema Miyazaki, Jun Yoshizawa, Hikari Noda, Yoshiteru Sakabe, Yoshiko Ichikawa, Ryoko Sekiya, Takao Fujii, Takuma Kurahashi, Hiroki |
author_facet | Ohwaki, Akiko Nishizawa, Haruki Kato, Asuka Kato, Takema Miyazaki, Jun Yoshizawa, Hikari Noda, Yoshiteru Sakabe, Yoshiko Ichikawa, Ryoko Sekiya, Takao Fujii, Takuma Kurahashi, Hiroki |
author_sort | Ohwaki, Akiko |
collection | PubMed |
description | BACKGROUND: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this association in a Japanese sample population. METHODS: The genotypes of three variants (rs4769613, rs12050029 and rs149427560) were examined in the upstream region of the FLT1 gene in placentas from pre-eclamptic (n=47) or normotensive control (n=49) pregnancy samples. Additionally, FLT1 mRNA levels in placenta were determined by qRT-PCR. ELISA was further used to detect circulating sFlt-1 levels in maternal sera. The intergroup comparisons were made using the Mann-Whitney U test or one way analysis of variance and P values of less than 0.05 were considered statistically significant. RESULTS: First, the rs4769613 (C>T) and rs12050029 (G>A) genotypes were examined in placentas but no significant differences were found in the genotype or allele-type frequencies. Next, nearby short tandem repeat, rs149427560, was examined which manifested four size variants. In the genotypewise analysis, the frequency of the 474/476 heterozygote was significantly lower in pre-eclampsia (p<0.05). As expected, the FLT1 mRNA levels were significantly elevated in the pre-eclamptic placentas and sFlt-1 was higher in pre-eclamptic maternal sera. However, the genotype of these variants did not affect the FLT1 mRNA or serum sFlt-1 levels. CONCLUSION: Our findings did not support the hypothesis that genetic variations around the FLT1 gene affect the subtle expression changes underlying the etiologic pathway of pre-eclampsia. The hypothesis deserves further investigation through a larger sample size. |
format | Online Article Text |
id | pubmed-7648866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Avicenna Research Institute |
record_format | MEDLINE/PubMed |
spelling | pubmed-76488662020-11-17 Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia Ohwaki, Akiko Nishizawa, Haruki Kato, Asuka Kato, Takema Miyazaki, Jun Yoshizawa, Hikari Noda, Yoshiteru Sakabe, Yoshiko Ichikawa, Ryoko Sekiya, Takao Fujii, Takuma Kurahashi, Hiroki J Reprod Infertil Original Article BACKGROUND: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this association in a Japanese sample population. METHODS: The genotypes of three variants (rs4769613, rs12050029 and rs149427560) were examined in the upstream region of the FLT1 gene in placentas from pre-eclamptic (n=47) or normotensive control (n=49) pregnancy samples. Additionally, FLT1 mRNA levels in placenta were determined by qRT-PCR. ELISA was further used to detect circulating sFlt-1 levels in maternal sera. The intergroup comparisons were made using the Mann-Whitney U test or one way analysis of variance and P values of less than 0.05 were considered statistically significant. RESULTS: First, the rs4769613 (C>T) and rs12050029 (G>A) genotypes were examined in placentas but no significant differences were found in the genotype or allele-type frequencies. Next, nearby short tandem repeat, rs149427560, was examined which manifested four size variants. In the genotypewise analysis, the frequency of the 474/476 heterozygote was significantly lower in pre-eclampsia (p<0.05). As expected, the FLT1 mRNA levels were significantly elevated in the pre-eclamptic placentas and sFlt-1 was higher in pre-eclamptic maternal sera. However, the genotype of these variants did not affect the FLT1 mRNA or serum sFlt-1 levels. CONCLUSION: Our findings did not support the hypothesis that genetic variations around the FLT1 gene affect the subtle expression changes underlying the etiologic pathway of pre-eclampsia. The hypothesis deserves further investigation through a larger sample size. Avicenna Research Institute 2020 /pmc/articles/PMC7648866/ /pubmed/33209740 http://dx.doi.org/10.18502/jri.v21i4.4328 Text en Copyright© 2020, Avicenna Research Institute. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Ohwaki, Akiko Nishizawa, Haruki Kato, Asuka Kato, Takema Miyazaki, Jun Yoshizawa, Hikari Noda, Yoshiteru Sakabe, Yoshiko Ichikawa, Ryoko Sekiya, Takao Fujii, Takuma Kurahashi, Hiroki Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title | Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title_full | Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title_fullStr | Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title_full_unstemmed | Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title_short | Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia |
title_sort | placental genetic variants in the upstream region of the flt1 gene in pre-eclampsia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648866/ https://www.ncbi.nlm.nih.gov/pubmed/33209740 http://dx.doi.org/10.18502/jri.v21i4.4328 |
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