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

项目摘要/摘要 这项拟议的研究将是第一个对非洲裔美国人(AA)普通人群进行的大型前瞻性研究。 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 最近的非洲血统个体，载脂蛋白L-1(Apol1)变体，与增加风险有关 再生障碍性贫血妇女中先兆子痫和/或早产的风险，这一人群患有两者的比例不成比例 条件。尽管再生障碍性贫血妇女因先兆子痫和早产而负担过重和死亡是众所周知的 出生，我们目前对先兆子痫和早产的遗传易感性的了解是初步的。 载脂蛋白L-1基因常见的编码变异已被证明是非常强烈的危险因素 腹主动脉硬化患者的肾脏疾病谱。这些位于22号染色体上的风险变异在慢性阻塞性肺疾病患者中高度流行 撒哈拉以南非洲，这是世界上先兆子痫和早产发生率最高的地区。几个 基础科学研究支持载脂蛋白1在子痫前期的病因学中的潜在作用 早产的病理生理学。然而，人类对APOL1基因的研究结果表明，APOL1基因有患糖尿病的风险 先兆子痫和早产是相互冲突的，并且依赖于相对较小的样本，这些样本相互冲突 结果。来自具有足够统计能力的再生障碍性贫血妇女普遍人群的流行病学证据 迫切需要填补关于APOL1基因是否使再生障碍性贫血女性患上更高性别的知识空白 先兆子痫和早产的风险。我们建议在一个较大的前瞻性队列中检验这些假设。 来自美国各地的AA女性，黑人女性健康研究(BWHS)。BWHS有25年的历史 纵向数据，重复收集关于怀孕、生育结局、生活方式因素和 病史，以及从29,601名妇女那里收集的生物样本。APOL1基因分型数据如下 已为9,355名BWHS参与者提供。我们建议另外对1,052个样本进行基因分型 并将使用2：1匹配的病例对照研究设计来检验我们的假设。 这项研究的发现将为先兆子痫和早产的复杂病理生理提供新的见解 在AAA中分娩，并有助于确定妊娠并发症的早期风险指标。两国之间的巨大差距 必须解决再生障碍性贫血妇女所经历的孕产妇发病率和死亡率问题。拟议的研究具有 可能提供的信息可用于更早地发现和可能预防某些 怀孕并发症。

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.