Hypoxia-Inducible Factor 1-Alpha Gene Polymorphisms Impact Risk of Severespectrum Hypertensive Disorders of Pregnancy: A Case-Control Study.

IF 2.6 3区 医学 Q2 OBSTETRICS & GYNECOLOGY Reproductive Sciences Pub Date : 2025-03-14 DOI:10.1007/s43032-025-01835-5
Claire Baldauf, Chen Wei, Trevor A Pickering, Brendan Grubbs, Håkon Gjessing, Melissa L Wilson
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Abstract

Hypoxia-inducible factor 1-alpha (HIF-1α) regulates cellular responses to hypoxia. Overexpression of HIF-1α is associated with abnormal placental trophoblast invasion and hypertensive disorders of pregnancy. We evaluated the putative association between polymorphisms and haplotypes in parental and child HIF-1α genes and the risk of severe-spectrum hypertensive disorders of pregnancy. Case (N = 179) and control (N = 34) mother-father-child triads were recruited by an internet-based method. Cases were defined as HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome or pre-eclampsia with severe features. Four HIF-1α single nucleotide polymorphisms were genotyped: rs4902080, rs2057492, rs11549465, rs10144958. Relative risks and 95% confidence intervals were estimated using log-linear free response models, adjusting for correlation between familial genotypes. Relative risk of severe-spectrum hypertensive disorder of pregnancy was increased with double-dose carriage of the T allele for SNP rs4902080 in both mother [RR 6.96, p = 0.028] and child [RR 5.77, p = 0.031]. Child double-dose of the T allele for SNP rs10144958 [RR 5.52, p = 0.047] also increased risk. The heterozygous genotype (CT) for SNPs rs2057482 and rs11549465 was protective against hypertensive disorders of pregnancy when carried by mother [rs2057482: RR 0.34, p < 0.001; rs11549465: RR 0.23, p < 0.001] or child [rs2057482: RR 0.44, p < 0.001; rs11549465: RR 0.31, p < 0.001]. A single copy of the C-c-c-G haplotype (rs4902080-rs2057482-rs11549465-rs10144958, N = 147), conferred decreased risk versus the C-T-T-G haplotype in mother [RR 0.28, p < 0.001] and child [RR 0.36, p < 0.001]. No parent-of-origin effects were seen. We conclude that polymorphism changes and haplotypes in the HIF-1α gene of mothers, fathers, and children are associated with risk for severe-spectrum hypertensive disorders of pregnancy.

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低氧诱导因子 1-α(HIF-1α)调节细胞对低氧的反应。HIF-1α的过度表达与胎盘滋养层异常侵袭和妊娠高血压疾病有关。我们评估了父母和子女 HIF-1α 基因的多态性和单倍型与严重妊娠高血压疾病风险之间的假定关联。通过互联网方法招募了病例(N = 179)和对照(N = 34)母-父-子三人组。病例被定义为 HELLP(溶血、肝酶升高和血小板低)综合征或具有严重特征的子痫前期。对四种 HIF-1α 单核苷酸多态性进行了基因分型:rs4902080、rs2057492、rs11549465 和 rs10144958。使用对数线性自由反应模型估算相对风险和 95% 置信区间,并对家族基因型之间的相关性进行调整。母亲[RR 6.96,p = 0.028]和儿童[RR 5.77,p = 0.031]双剂量携带 SNP rs4902080 的 T 等位基因会增加患严重妊娠高血压疾病的相对风险。儿童双剂量 SNP rs10144958 的 T 等位基因[RR 5.52,p = 0.047]也会增加风险。母亲携带 SNP rs2057482 和 rs11549465 的杂合基因型(CT)对妊娠高血压疾病有保护作用[rs2057482:RR:0.34,p
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来源期刊
Reproductive Sciences
Reproductive Sciences 医学-妇产科学
CiteScore
5.50
自引率
3.40%
发文量
322
审稿时长
4-8 weeks
期刊介绍: Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.
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