Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk

Hong, Xiumei; Rosenberg, Avi Z.; Zhang, Boyang; Binns-Roemer, Elizabeth; David, Victor A.; Lv, Yiming; Hjorten, Rebecca; Reidy, Kimberly; Chen, Teresa K.; Wang, Guoying; Ji, Yuelong; Simpson, Claire L.; Davis, Robert L.; Kopp, Jeffrey B.; Wang, Xiaobin; Winkler, Cheryl A.

doi:10.1053/j.ajkd.2020.10.020

Cited by 21 publications

(24 citation statements)

References 40 publications

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“…Overall, our observations were consistent with previous reports that fetal APOL1 genotype contributes to elevated PE risk [9–11]. We observed an association of fetal APOL1 risk genotypes with PE in preterm cases in both recessive and additive inheritance models.…”

Section: Discussionsupporting

confidence: 93%

“…In prior studies of PE, findings differed on the impact of the maternal APOL1 genotype [8] and the observed model of inheritance [9, 10]. Most recently, a study reported increased PE risk in African Americans associated with a recessive model of the fetal APOL1 genotype and with maternal-fetal APOL1 genotype discordance [11]. These inconsistencies in the observed model of inheritance and the role of maternal versus fetal genotype leave several important questions related to the mode of action of the APOL1 risk alleles on PE unanswered.…”

Section: Introductionmentioning

confidence: 99%

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Fetal High-Risk APOL1 Genotype Increases Risk for Small for Gestational Age in Term Infants Affected by Preeclampsia

et al. 2023

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Background: Hypertensive disorders of pregnancy cause fetal growth restriction and increased maternal morbidity and mortality, especially in women of African ancestry. Recently, preeclampsia risk was associated with polymorphisms in the apolipoprotein L1 (APOL1) gene in women of African ancestry. Objectives: We assessed APOL1 genotype effects on pregnancies with and without preeclampsia. Method: We conducted an unmatched case-control study of 1,358 mother-infant pairs from two independent cohorts of black women. Results: Term preeclampsia cases with high-risk APOL1 genotypes were more likely to be small for gestational age compared to APOL1 low-risk term cases (odds ratio [OR] 2.8) and APOL1 high-risk controls (OR 5.5). Among preterm pregnancies, fetal APOL1 genotype was associated with preeclampsia. Conclusions: Fetal APOL1 genotype was associated with preeclampsia in preterm infants and with altered fetal growth in term infants. This may indicate APOL1 genotype impacts a spectrum of pregnancy complications mediated by a common pathophysiological event of placental insufficiency.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Fetal High-Risk APOL1 Genotype Increases Risk for Small for Gestational Age in Term Infants Affected by Preeclampsia

et al. 2023

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“…A 2018 study reported that although maternal APOL1 risk genotype was not associated with preeclampsia, mothers of fetuses with two APOL1 risk alleles had a higher risk of preeclampsia than mothers of fetuses with low-risk alleles 14 , with an odds ratio of 1.8. This finding was confirmed and extended in a second study, which also found that APOL1 allelic mismatch between fetus and mother was associated with nearly three-fold increased odds of preeclampsia 100 . However, and as described earlier, a study of APOL1 transgenic mice showed an eclampsia-like phenotype to be associated with the G2 risk allele and also unexpectedly with the G0 genotype; the effect of the G1 risk allele was not studied 78 .…”

Section: Apol1 Disease Associations Beyond Kidneysupporting

confidence: 54%

The evolving story of apolipoprotein L1 nephropathy: the end of the beginning

et al. 2022

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Genetic coding variants in APOL1 , which encodes apolipoprotein L1 (APOL1), were identified in 2010 and are relatively common among individuals of sub-Saharan African ancestry. Approximately 13% of African Americans carry two APOL1 risk alleles. These variants, termed G1 and G2, are a frequent cause of kidney disease — termed APOL1 nephropathy — that typically manifests as focal segmental glomerulosclerosis and the clinical syndrome of hypertension and arterionephrosclerosis. Cell culture studies suggest that APOL1 variants cause cell dysfunction through several processes, including alterations in cation channel activity, inflammasome activation, increased endoplasmic reticulum stress, activation of protein kinase R, mitochondrial dysfunction and disruption of APOL1 ubiquitinylation. Risk of APOL1 nephropathy is mostly confined to individuals with two APOL1 risk variants. However, only a minority of individuals with two APOL1 risk alleles develop kidney disease, suggesting the need for a ‘second hit’. The best recognized factor responsible for this ‘second hit’ is a chronic viral infection, particularly HIV-1, resulting in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor. Current therapies for APOL1 nephropathies are not adequate to halt progression of chronic kidney disease, and new targeted molecular therapies are in clinical trials.

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“…43,44 In 3 independent studies, the HR genotype was associated with increased odds of preeclampsia in African Americans (odds ratio, 1.4-3.3), 2 under a recessive model and 1 under a dominant model. 4,43,45 In each study, risk was conferred by the genotype of the fetus. The mother's country of origin (United States vs. Haiti) and discordance between maternal and fetal APOL1 genotype seemed to modify the association.…”

Section: Clinical Phenotypesmentioning

confidence: 99%