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: 10196602
• 负责人: Shanshan Sheehy
• 金额: $ 30.44万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10196602
• 关键词: Address; Affect; Africa South of the Sahara; African; African American; 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; 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.

项目摘要/摘要 拟议的研究将是非裔美国人一般人口的首次大型前瞻性研究（AA） 妇女要解决一个关键的未知数 - 是否观察到中等常见的突变 最近非洲血统，载脂蛋白L-1（APOL1）变体的个体与风险增加有关 AA妇女中的先兆子痫和/或早产的人口，这两者都遭受了不成比例的遭受 状况。尽管众所周知的过量烧伤和AA女性因先兆子痫和早产而死亡 生日，我们目前对遗传倾向的遗传倾向和早产是基本的。 载脂蛋白L-1基因中的常见编码变体已被证明是非常强的风险因素 AAS中的肾脏疾病频谱。这些在22号染色体上的风险变体在来自 撒哈拉以南非洲地区，这个地区的前启示性和早产率最高。一些 基础科学的研究支持APOL1在先兆子痫的病因中的潜在作用 早产的病理生理学。但是，人类对APOL1基因型的研究结果，风险 子痫前期和早产是矛盾的，并且对相对较小的样本有着可靠的矛盾 结果。来自具有足够统计能力的广义AA妇女人口的流行病学证据 迫切需要填补APOL1基因型是否使AA女性较高的知识差距 子痫前期和早产的风险。我们建议在大量前瞻性队列中检验这些假设 来自美国各地的AA妇女，黑人妇女健康研究（BWHS）。 BWHS有25年 纵向数据，并反复收集有关怀孕，出生结果，生活方式因素和 病史，除了从29,601名女性中收集的生物循环样本外。 Apol1基因型数据是 已经可用于9,355个BWHS参与者。我们建议从中额外从基因型中进行1,052个样本 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。 这项研究的发现将增加有关先兆子痫和早产的复杂病理生理学的新见解 AAS的出生，并有助于确定怀孕并发症的早期风险指标。巨大的差距 必须解决AA妇女经历的孕产妇发病率和死亡率。拟议的研究具有 提供可用于告知早期检测并可能预防某些信息的潜力 怀孕并发症。