Novel association between FOXO3 rs2232365 polymorphism and late-onset preeclampsia: a case-control candidate genetic stu
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RESEARCH ARTICLE
Open Access
Novel association between FOXO3 rs2232365 polymorphism and late-onset preeclampsia: a case-control candidate genetic study Xuefeng Pan1†, Benjie Wei2†, Hong Wang1, Lingyu Ma1, Zhaoli Du2 and Ying Chen1*
Abstract Background: Both genetic susceptibility and dysregulated lipid metabolism are important susceptibilities to preeclampsia. In the study, we devote to investigate the associations of FOXO3 and TLR7 genetic polymorphisms with preeclampsia in a Chinese population. Methods: This case-control study involved 335 Han Chinese pregnant women, including 177 pregnant women with preeclampsia and 158 healthy controls. The preeclampsia group was further sub-grouped into early-onset preeclampsia (EOPE, n = 70)and late-onset preeclampsia (LOPE, n = 107. Three single nucleotide polymorphisms (SNPs), including FOXO3 (rs2232365, rs3761548), and TLR7 rs3853839 were genotyped by multiplex PCR for targeted next-generation sequencing. The χ2 test and multiple interaction effect analyses were performed to determine the association of three SNPs with serum lipid levels and thyroid function in women with preeclampsia. Results: The genotype (CC vs. TT + CT) distribution of rs2232365 revealed a significant association with LOPE (P = 0.004, odds ratio = 3.525 (0.95 CI: 1.498–8.164)). No significant difference was found in the genotype and allele frequencies of rs3761548 and rs3853839 between controls and cases (P > 0.05). Moreover, the genotype CT/TT of rs2232365 was significantly correlated with increased TG/HDL levels in the LOPE group (p = 0.014). Conclusions: The polymorphisms of rs2232365 are associated with the risk of LOPE and may modulate TG/HDL levels in pregnant women with LOPE. Keywords: Preeclampsia, Single nucleotide polymorphism, rs2232365, BMI, Lipid metabolism
Introduction Preeclampsia (PE) is a pregnancy-specific syndrome and associated with significant maternal and fetal morbidity and mortality [1]. PE averagely affects 6.7% of pregnant women globally and 4.2% individuals in China [2, 3]. The pathogenesis of PE is multifactorial, with acknowledged * Correspondence: [email protected] † Xuefeng Pan and Benjie Wei contributed equally to this work. 1 Department of Obstetrics, The First Hospital of Jilin University, Xinmin Street 1, Changchun, Jilin Province 130021, China Full list of author information is available at the end of the article
contributions by genetic susceptibility, inflammatory stimuli, metabolic syndrome, oxidative stress, placental, and vascular dysfunction [4]. According to epidemiological studies, there was a high prevalence of metabolic syndrome in women with PE [5], otherwise autoimmune diseases and dysregulated lipid metabolism showed a tight association [6]. One of these most important hypotheses of PE is that maternal adequate immunological response is necessary to the existence of the fetus in pregnancy [7]. Forkhead/winged helix transcription factor(FoxP3)is the key transcription factor for Regulatory T cells (Tregs)
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