Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia

Authors
Akiko Ohwaki 1
Haruki Nishizawa 2
Asuka Kato 2
Takema Kato 3
Jun Miyazaki 1
Hikari Yoshizawa 1
Yoshiteru Noda 1
Yoshiko Sakabe 1
Ryoko Ichikawa 2
Takao Sekiya 2
Takuma Fujii 2
Hiroki Kurahashi 3
1 Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan; Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan
2 Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan
3 Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan
10.18502/jri.v21i4.4328
Abstract
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.
Keywords
FLT1
placenta
Pre
Eclampsia
Short Tandem Repeat
Single nucleotide variant
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Journal of Reproduction & Infertility
Volume 21, Issue 4
Autumn 2020
Pages 240-246