Apolipoprotein L1 variants and risk of preeclampsia and preterm birth in African American women

载脂蛋白 L1 变异与非裔美国女性先兆子痫和早产的风险

• 批准号: 10396600
• 负责人: Shanshan Sheehy
• 金额: $ 16.56万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396600
• 关键词: Address; Affect; Africa South of the Sahara; African American; African American population; African ancestry; Animals; Apolipoproteins; Area; Basic Science; Birth; Cessation of life; Chromosome 22; Chronic Kidney Failure; Code; Complex; Conflict (Psychology); Data; Data Analyses; Data Set; Early Diagnosis; Epidemiology; Etiology; Functional disorder; Future; General Population; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Health; Human; Individual; Kidney Diseases; Knowledge; Lead; Matched Case-Control Study; Maternal Mortality; Medical History; Messenger RNA; Mutation; Outcome; Participant; Persons; Placenta; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Rate; Premature Birth; Prevention; Prospective Studies; Prospective cohort; Proteins; Publishing; Recommendation; Reproductive Health; Research; Research Design; Risk; Risk Factors; Role; Sample Size; Sampling; Serum; Suggestion; Testing; Transgenic Mice; United States; Variant; Woman; Women' s Health; adverse pregnancy outcome; base; black women; experience; fetal; high risk; insight; lifestyle factors; maternal morbidity; men; mouse model; neonatal death; pathophysiology of preeclampsia; pregnant; public health relevance; racial disparity; risk variant

PROJECT SUMMARY/ABSTRACT The proposed study will be the first large prospective study from a general population of African American (AA) women to address a critical unknown—whether the moderately common mutations only observed among individuals of recent African ancestry, apolipoprotein L-1 (APOL1) variants, are associated with increased risk of preeclampsia and/or preterm birth among AA women, a population that disproportionally suffers from both conditions. Despite the well-known excess burden and deaths in AA women from preeclampsia and preterm birth, our current understanding of genetic predisposition to preeclampsia and preterm birth is rudimentary. Common coding variants in the apolipoprotein L-1 gene have been shown to be very strong risk factors for a spectrum of kidney disease in AAs. These risk variants on chromosome 22 are highly prevalent in people from Sub-Saharan Africa, an area with the highest rate of preeclampsia and preterm birth worldwide. Several studies in basic science support a potential role of APOL1 in the etiology of preeclampsia and the pathophysiology of preterm birth. However, results of human studies on APOL1 genotype with risk of preeclampsia and preterm birth are conflicting and have relied on relatively small samples with conflicting results. Epidemiological evidence from a generalized population of AA women with sufficient statistical power is urgently needed to fill the knowledge gap of whether APOL1 genotype predisposes AA women to a higher risk of preeclampsia and preterm birth. We propose to test these hypotheses in a large prospective cohort of AA women from across the United States, the Black Women's Health Study (BWHS). The BWHS has 25 years of longitudinal data, with repeatedly collected information on pregnancy, birth outcomes, lifestyle factors, and medical history, in addition to biospecimen samples collected from 29,601 women. APOL1 genotype data are already available for 9,355 BWHS participants. We propose to additionally genotype 1,052 samples from women with preeclampsia and will use a 2:1 matched case-control study design to test our hypothesis. Findings from this study will add new insights on the complex pathophysiology of preeclampsia and preterm birth among AAs, and help to identify early risk indicators for pregnancy complications. The huge disparity in maternal morbidity and mortality experienced by AA women must be addressed. The proposed study has the potential to provide information that can be used to inform earlier detection and possible prevention of certain pregnancy complications.

项目概要/摘要 拟议的研究将是第一项针对非裔美国人 (AA) 一般人群的大型前瞻性研究 女性要解决一个关键的未知问题——中等常见的突变是否只在人群中观察到 近代非洲血统的个体，载脂蛋白 L-1 (APOL1) 变体与风险增加相关 AA 女性中先兆子痫和/或早产的发生率，这一人群中患有这两种疾病的比例不成比例 状况。尽管 AA 妇女因先兆子痫和早产而造成的过度负担和死亡是众所周知的 出生后，我们目前对先兆子痫和早产遗传倾向的了解​​还很初级。 载脂蛋白 L-1 基因中常见的编码变异已被证明是非常强烈的危险因素。 AA 中肾脏疾病的谱系。 22 号染色体上的这些风险变异在以下人群中非常普遍： 撒哈拉以南非洲地区是全球先兆子痫和早产率最高的地区。一些 基础科学研究支持 APOL1 在先兆子痫的病因学中的潜在作用以及 早产的病理生理学。然而，对 APOL1 基因型的人体研究结果显示，存在以下风险： 先兆子痫和早产是相互矛盾的，并且依赖于相对较小的样本 结果。来自一般 AA 女性人群的流行病学证据，具有足够的统计能力 迫切需要填补 APOL1 基因型是否使 AA 女性更容易获得更高水平的知识空白 先兆子痫和早产的风险。我们建议在一个大型前瞻性队列中测试这些假设 来自美国各地的 AA 女性黑人女性健康研究 (BWHS)。 BWHS 已有 25 年历史 纵向数据，反复收集有关怀孕、出生结果、生活方式因素和 病史，以及从 29,601 名女性采集的生物样本样本。 APOL1 基因型数据是 已可供 9,355 名 BWHS 参与者使用。我们建议对来自以下国家的 1,052 个样本进行额外基因分型： 患有先兆子痫的女性将使用 2:1 匹配的病例对照研究设计来检验我们的假设。 这项研究的结果将为先兆子痫和早产的复杂病理生理学提供新的见解 AA 中的出生，并有助于识别妊娠并发症的早期风险指标。巨大的差距在于 必须解决 AA 妇女所经历的孕产妇发病率和死亡率问题。拟议的研究有 提供可用于早期发现和可能预防某些疾病的信息的潜力 妊娠并发症。