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非裔美国人中先兆子痫与婴儿载脂蛋白L1(APOL1)基因型的关联。

Association of preeclampsia with infant APOL1 genotype in African Americans.

作者信息

Miller Anna K, Azhibekov Timur, O'Toole John F, Sedor John R, Williams Scott M, Redline Raymond W, Bruggeman Leslie A

机构信息

Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, USA.

Division of Neonatology, Department of Pediatrics, Metro Health Medical Center, Case Western Reserve University School of Medicine, Cleveland, USA.

出版信息

BMC Med Genet. 2020 May 20;21(1):110. doi: 10.1186/s12881-020-01048-4.

Abstract

BACKGROUND

Black women in the United States and Africa are at an increased risk for preeclampsia. Allelic variants in the gene for apolipoprotein LI, APOL1, are found only in populations of African ancestry, and have been shown to contribute significant risk for kidney disease. Recent studies suggest these APOL1 variants also may contribute risk for preeclampsia.

METHODS

The association of preeclampsia with carriage of APOL1 risk alleles was evaluated in a case-control study of deliveries from black women at a single center in Cleveland, Ohio that included gross and histopathologic evaluations of placental tissues (395 cases and 282 controls). Using logistic regression models, associations between fetal APOL1 genotype and preeclampsia were evaluated using several case definitions based on prematurity and severity of preeclampsia, with uncomplicated term pregnancies as controls. Associations between APOL1 genotype and pathological features were also examined.

RESULTS

The infant APOL1 genotype was significantly associated with preeclampsia in a dominant inheritance pattern with odds ratio of 1.41 (P=0.029, 95% CI 1.037, 1.926). Stratifying preeclampsia cases by preterm birth, significant associations were detected for both recessive (O.R.=1.70, P=0.038) and additive (O.R.=1.33, P=0.028) inheritance patterns. APOL1 genotype, however, was not significantly associated with pathological changes or other perinatal observations.

CONCLUSIONS

Preeclampsia appears to be another disease associated with APOL1 variants, however, further studies are needed to increase confidence in the mode of inheritance. By understanding the association of APOL1 variants with preeclampsia, genetic screening tests for APOL1 may be useful to predict at-risk pregnancies and targeted interventions may be developed to improve pregnancy outcomes.

摘要

背景

美国和非洲的黑人女性患先兆子痫的风险增加。载脂蛋白L1(APOL1)基因的等位基因变异仅在非洲裔人群中发现,并已被证明会显著增加患肾病的风险。最近的研究表明,这些APOL1变异也可能增加先兆子痫的风险。

方法

在俄亥俄州克利夫兰市一个单一中心对黑人女性分娩进行的病例对照研究中,评估了先兆子痫与携带APOL1风险等位基因之间的关联,该研究包括对胎盘组织的大体和组织病理学评估(395例病例和282例对照)。使用逻辑回归模型,根据先兆子痫的早产情况和严重程度,采用几种病例定义,以无并发症的足月妊娠作为对照,评估胎儿APOL1基因型与先兆子痫之间的关联。还检查了APOL1基因型与病理特征之间的关联。

结果

婴儿APOL1基因型与先兆子痫呈显著的显性遗传模式相关,优势比为1.41(P=0.029,95%可信区间1.037,1.926)。按早产情况对先兆子痫病例进行分层,发现隐性(优势比=1.70,P=0.038)和加性(优势比=1.33,P=0.028)遗传模式均有显著关联。然而,APOL1基因型与病理变化或其他围产期观察结果无显著关联。

结论

先兆子痫似乎是另一种与APOL1变异相关的疾病,然而,需要进一步研究以增强对遗传模式的信心。通过了解APOL1变异与先兆子痫的关联,APOL1基因筛查测试可能有助于预测高危妊娠,并可能制定针对性干预措施以改善妊娠结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360e/7238556/aec433e7a922/12881_2020_1048_Fig1_HTML.jpg

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