Association between Apolipoprotein L1 genetic variants and risk of preeclampsia and preterm birth among U.S. Black women

Abstract

Background: Preeclampsia and preterm birth disproportionally affects Black women, but the current understanding of genetic predisposition to preeclampsia and preterm birth is rudimentary. It has been hypothesized that carriers of high-risk genetic variants in the apolipoprotein L1 gene (APOL1) may have an increased risk of preeclampsia and preterm birth. These genetic variants are found only among individuals of recent African ancestry. Previous studies have been small and have yielded inconsistent results. Objective: To examine whether APOL1 genetic variants are associated with risk of preeclampsia or preterm birth. Study design: We conducted a retrospective case-control study of 6616 Black women from the Black Women’s Health Study, a cohort of self-identified Black women in the U.S. Genotype data on APOL1 risk alleles for this case control study were obtained through new genotyping and existing genetic data from a prior case control study of breast cancer using the Illumina Infinium Global Diversity Array or Multi Ethnic Genotyping Array. Primary analyses evaluated risk based on a recessive model, comparing women who carried two APOL1 risk alleles to women who carried zero or one risk allele. We used multivariable logistic regression models to examine associations among 1473 participants with a history of preeclampsia (cases) and 5143 parous women who had not experienced preeclampsia (controls), and among 1296 participants who had a history of preterm birth and 5320 without such history. Results: The odds ratio (OR) of preeclampsia for two APOL1 risk alleles vs. zero or one risk allele was 0.99 (95 % confidence interval (CI): 0.74, 1.32) after adjustment for principal components, genotype platform, and age in 1995. For preterm birth, the comparable multivariable OR was 1.04 (95 % CI: 0.86, 1.25). Conclusions: This large prospective study from a general population of Black women found no evidence of an association of APOL1 genotype with risk of either preeclampsia or preterm birth.

Keywords

• Apolipoprotein L1
• Preeclampsia
• Preterm birth
• Black American