Abstract
Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case–control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease.
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The authors thank all the participants participating in the study.
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This work was funded by grants from National Natural Science Foundation of China (Grant No. 81801613, 81702276), China Postdoctoral Fund (Grant No. 2020M682188), Shandong Provincial Natural Science Foundation (Grant No. ZR2021LZY009, ZR2020QH052 and ZR2019PC047), Science and Technology Development Plan of Jinan (Grant No. 202019090).
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QX contributed to the conception of the study and wrote the manuscript. YH, JW and WJ performed the experiment. YL and QJ contributed significantly to analysis and manuscript preparation. WS performed the data analyses and helped perform the analysis with constructive discussions.
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Xin, Q., Han, Y., Jiang, W. et al. Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population. Mol Genet Genomics 297, 791–800 (2022). https://doi.org/10.1007/s00438-022-01889-z
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DOI: https://doi.org/10.1007/s00438-022-01889-z