TY - JOUR T1 - Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia T2 - Journal of Reproduction & Infertility JT - Journal of Reproduction & Infertility SP - 240 EP - 247 VL - 21 IS - 4 PY - 2020 SN - 2251-676X L1 - https://www.jri.ir/documents/fullpaper/en/90089.pdf L2 - https://www.jri.ir/article/90089 UR - https://www.jri.ir/en/currentissue.aspx?id=85 PB - Avicenna Research Institute AU - Ohwaki, Akiko AU - Nishizawa, Haruki AU - Kato, Asuka AU - Kato, Takema AU - Miyazaki, Jun AU - Yoshizawa, Hikari AU - Noda, Yoshiteru AU - Sakabe, Yoshiko AU - Ichikawa, Ryoko AU - Sekiya, Takao AU - Fujii, Takuma AU - Kurahashi, Hiroki AB -

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.

CY - Tehran, Iran LA - English