An investigation of APOL1 risk genotypes and preterm birth in African American population cohorts
An investigation of APOL1 risk genotypes and preterm birth in African American population cohorts
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DOI：
10.1093/ndt/gfw317
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发表时间：
2017-12-01
影响因子：
6.1
通讯作者：
Sampson, Matthew G.
中科院分区：
文献类型：
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作者：
Robertson, Catherine C.;Gillies, Christopher E.;Sampson, Matthew G.
背景载脂蛋白L1（APOL 1）的两种遗传变异与局灶节段性肾小球硬化症以及其他肾小球表型的风险增加相关。这些风险变异在非洲血统的个体中很常见，但在其他种族群体中不存在。然而，大多数具有两个APOL 1风险等位基因[高风险（HR）基因型]的个体没有肾脏疾病。关键是要确定环境和继发性遗传影响，当与这些等位基因结合时，导致肾脏疾病。在最近的一项对肾病综合征研究网络（NEPTUNE）和儿童慢性肾病研究（n = 104）中登记的患有肾小球疾病的黑人儿童的研究中，我们发现，与低风险（LR）基因型相比，HR基因型的受试者早产的几率增加了4.6倍[比值比4.6（CI 1.4-15.5）]。在早产方面存在已知的种族差异，早产本身是慢性肾病和局灶节段性肾小球硬化症的已知风险因素。因此，我们质疑HR APOL 1基因型是否与非裔美国人的早产有关。我们分析了非裔美国人早产的两个临床可用的遗传数据集，包括来自基因环境协会研究（日内瓦）早产研究的867名婴儿和519名母亲以及来自波士顿医学中心早产全基因组关联研究的960名母亲。我们对HR APOL 1和出生结局之间的关系进行了多变量分析。在这两项研究中，母亲的HR APOL 1与早产、胎龄或出生体重之间没有关联。此外，在日内瓦研究中，我们没有发现婴儿HR APOL 1与早产、胎龄或出生体重之间存在关联。从这些数据中，我们得出结论，以前观察到的HR APOL 1和早产之间的关联是特定于肾小球疾病，这表明早产可能是APOL 1相关肾脏疾病的额外风险因素。
Background. Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes. These risk variants are common in individuals of African ancestry but absent in other racial groups. Yet, the majority of individuals with two APOL1 risk alleles [high-risk (HR) genotype] do not have renal disease. It is critical to identify environmental and secondary genetic influences that, when combined with these alleles, lead to kidney disease. In a recent study of black children with glomerular disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) and Chronic Kidney Disease in Children Study (n = 104), we found that subjects with an HR genotype had a 4.6-fold increase in the odds of preterm birth as compared to those with a low risk (LR) genotype [odds ratio 4.6 (CI 1.4-15.5)]. There are known racial disparities in preterm birth, which itself is a known risk factor for chronic kidney disease and focal segmental glomerulosclerosis. Thus, we questioned whether an HR APOL1 genotype isassociated with prematurity in the general African American population.Methods. We analyzed two publically available genetic datasets of preterm birth in African Americans, including 867 infants and 519 mothers from the Gene Environment Association Studies (GENEVA) study of preterm delivery and 960 mothers from the Boston Medical Center genome-wide association study of preterm birth. We performed multivariable analyses testing for association between HR APOL1 and birth outcomes.Results. In both studies, there was no association between HR APOL1 in mothers and prematurity, gestational age or birthweight. Additionally, in the GENEVA study, we saw no association between infant HR APOL1 and prematurity, gestational age or birthweight.Conclusion. From these data, we conclude that the previously observed association between HR APOL1 and prematurity is specific to those with glomerular disease, suggesting prematurity may act as an additional risk factor in APOL1-associated renal disease.