可溶性Fms样酪氨酸激酶-1基因多态性与重度妊娠期高血压疾病相关。
Soluble Fms-like tyrosine kinase-1 polymorphisms associated with severe-spectrum hypertensive disorders of pregnancy.
作者信息
Chen Tracy, Baldauf Claire E, Gill Kevin S, Ingles Sue Ann, Pickering Trevor A, Wilson Melissa L
机构信息
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA.
Fetal and Neonatal Institute, Division of Neonatology, Department of Pediatrics, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
出版信息
Arch Gynecol Obstet. 2025 Mar;311(3):609-619. doi: 10.1007/s00404-024-07917-0. Epub 2025 Jan 13.
BACKGROUND
sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.
METHODS
Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH). Cases of severe disease (99) and controls (31) from mother-father-baby triads were recruited through HELLP syndrome websites. Four sFLT-1 SNPs (rs7993594, rs3751395, rs7983774, and rs664393) were genotyped. Data was analyzed using a log-linear regression model in the Haplin package in R.
RESULTS
Maternal double dose of the A allele (rs7993594) exhibited a nominally significant increased risk of HDP (RR = 3.52, 95% CI 1.08, 11.20). In the severe-spectrum cohort, a marginally significant protective effect among mothers carrying infants with a single dose of the A allele (rs7993594) was observed (RR = 0.59, 95% CI 0.36, 0.98) and double-dose maternal carriage of the G-t-G-G haplotype increased risk of severe disease (RR = 4.13, 95% CI 1.22, 13.80).
CONCLUSION
The maternal rs7993594 A allele appears to be associated with increased risk of HDP. Double-dose maternal carriage of the G-t-G-G haplotype increased risk of severe disease whereas the fetal rs7983774 A allele appears to be associated with decreased risk.
背景
可溶性血管内皮生长因子受体-1（sFLT-1）与妊娠期高血压疾病（HDP）的发病机制有关。我们旨在研究母体和胎儿基因多态性在HDP及严重程度疾病风险中的作用。
方法
在洛杉矶县妇女儿童医院（WCH）招募母婴二元组中的HDP病例（143例）和对照（169例）。通过HELLP综合征网站招募母婴父三元组中的严重疾病病例（99例）和对照（31例）。对4个sFLT-1单核苷酸多态性（SNP，rs7993594、rs3751395、rs7983774和rs664393）进行基因分型。使用R语言中Haplin软件包的对数线性回归模型分析数据。
结果
母体携带双剂量A等位基因（rs7993594）患HDP的风险名义上显著增加（相对风险[RR]=3.52，95%置信区间[CI]1.08，11.20）。在严重程度疾病队列中，观察到携带单剂量A等位基因（rs7993594）婴儿的母亲有边缘显著的保护作用（RR=0.59，95%CI 0.36，0.98），而母体携带双剂量G-t-G-G单倍型会增加严重疾病风险（RR=4.13，95%CI 1.22，13.80）。
结论
母体rs7993594 A等位基因似乎与HDP风险增加有关。母体携带双剂量G-t-G-G单倍型会增加严重疾病风险，而胎儿rs7983774 A等位基因似乎与风险降低有关。
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