Sheehy Shanshan, Friedman David, Liu Chunyu, Lunetta Kathryn L, Zirpoli Gary, Palmer Julie R
Slone Epidemiology Center, Boston University, USA.
Beth Israel Deaconess Medical Center, USA.
Eur J Obstet Gynecol Reprod Biol X. 2025 Jan 9;25:100365. doi: 10.1016/j.eurox.2025.100365. eCollection 2025 Mar.
Preeclampsia and preterm birth disproportionally affects Black women, but the current understanding of genetic predisposition to preeclampsia and preterm birth is rudimentary. It has been hypothesized that carriers of high-risk genetic variants in the apolipoprotein L1 gene () may have an increased risk of preeclampsia and preterm birth. These genetic variants are found only among individuals of recent African ancestry. Previous studies have been small and have yielded inconsistent results.
To examine whether genetic variants are associated with risk of preeclampsia or preterm birth.
We conducted a retrospective case-control study of 6616 Black women from the Black Women's Health Study, a cohort of self-identified Black women in the U.S. Genotype data on risk alleles for this case control study were obtained through new genotyping and existing genetic data from a prior case control study of breast cancer using the Illumina Infinium Global Diversity Array or Multi Ethnic Genotyping Array. Primary analyses evaluated risk based on a recessive model, comparing women who carried two risk alleles to women who carried zero or one risk allele. We used multivariable logistic regression models to examine associations among 1473 participants with a history of preeclampsia (cases) and 5143 parous women who had not experienced preeclampsia (controls), and among 1296 participants who had a history of preterm birth and 5320 without such history.
The odds ratio (OR) of preeclampsia for two risk alleles vs. zero or one risk allele was 0.99 (95 % confidence interval (CI): 0.74, 1.32) after adjustment for principal components, genotype platform, and age in 1995. For preterm birth, the comparable multivariable OR was 1.04 (95 % CI: 0.86, 1.25).
This large prospective study from a general population of Black women found no evidence of an association of genotype with risk of either preeclampsia or preterm birth.
子痫前期和早产对黑人女性的影响尤为严重，但目前对子痫前期和早产的遗传易感性的了解还很基础。有假说认为，载脂蛋白L1基因（）中高危基因变异的携带者患子痫前期和早产的风险可能会增加。这些基因变异仅在近期有非洲血统的个体中发现。以往的研究规模较小，结果也不一致。
研究基因变异是否与子痫前期或早产风险相关。
我们对来自黑人女性健康研究的6616名黑人女性进行了一项回顾性病例对照研究，该研究是美国一个自我认定为黑人女性的队列。通过新的基因分型以及先前一项乳腺癌病例对照研究中使用Illumina Infinium全球多样性阵列或多民族基因分型阵列的现有基因数据，获得了该病例对照研究中风险等位基因的基因型数据。主要分析基于隐性模型评估风险，将携带两个风险等位基因的女性与携带零个或一个风险等位基因的女性进行比较。我们使用多变量逻辑回归模型来研究1473例子痫前期病史参与者（病例组）和5143例未经历子痫前期的经产妇（对照组）之间的关联，以及1296例有早产病史的参与者和5320例无此类病史的参与者之间的关联。
在对主成分、基因型平台和1995年年龄进行调整后，两个风险等位基因与零个或一个风险等位基因相比，子痫前期的优势比（OR）为0.99（95%置信区间（CI）：0.74，1.32）。对于早产，可比的多变量OR为1.04（95%CI：0.86，1.25）。
这项来自黑人女性普通人群的大型前瞻性研究没有发现基因与子痫前期或早产风险之间存在关联的证据。
