Fetal—Not Maternal—APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry

Kimberly J. Reidy, Rebecca C. Hjorten, Claire Simpson, Avi Z. Rosenberg, Stacy D. Rosenblum, Csaba Kovesdy, Frances Tylavsky, Joseph Myrie, Bianca L. Ruiz, Soulin Haque, Khyobeni Mozhui, George W. Nelson, Victor A. David, Xiaoping Yang, Masako Suzuki, Jack Jacob, Sandra E. Reznik, Frederick J. Kaskel, Jeffrey B. Kopp, Cheryl A. Winkler & 1 others Robert Davis

Research output: Contribution to journalArticle

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Abstract

Black Americans are at increased risk for preeclampsia. Genetic variants in apolipoprotein L1 (APOL1) account for much of the increased risk for kidney disease in blacks. APOL1 is expressed in human placenta and transgenic mice expressing APOL1 develop preeclampsia. We evaluated the role of APOL1 variants in human preeclampsia. We determined maternal and fetal APOL1 genotypes in black women with preeclampsia in two populations. At Einstein Montefiore Center (EMC) Affiliated Hospitals, we studied 121 pregnancies in black women with preeclampsia. At University of Tennessee Health Science Center (UTHSC), we studied 93 pregnancies in black women with preeclampsia and 793 pregnancies without preeclampsia. We measured serum markers of preeclampsia soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Fetal APOL1 high-risk (HR) genotype was associated with preeclampsia, with odds ratios at EMC and UTHSC of 1.84 (95% CI 1.11, 2.93) and 1.92 (95% CI 1.05, 3.49), respectively. Maternal APOL1 HR genotype was not associated with preeclampsia. Mothers with the fetal APOL1 HR genotype had more cerebral or visual disturbances (63% versus 37%, p = 0.04). In addition, fetal APOL1 HR genotype was associated with a higher sFLT-1/PlGF ratio at birth (p = 0.04). Fetal APOL1 high-risk genotype increases the risk for preeclampsia, likely by adversely affecting placental function. Further research is needed to assess whether APOL1 genetic testing can predict preeclampsia and improve pregnancy outcomes.

Original languageEnglish (US)
Pages (from-to)367-376
Number of pages10
JournalAmerican Journal of Human Genetics
Volume103
Issue number3
DOIs
StatePublished - Sep 6 2018

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Apolipoproteins
Pre-Eclampsia
Genotype
Mothers
Pregnancy
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor Receptor-1
Health
Kidney Diseases
Genetic Testing
Pregnancy Outcome
Placenta
Transgenic Mice
Biomarkers
Odds Ratio
Parturition

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Fetal—Not Maternal—APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry. / Reidy, Kimberly J.; Hjorten, Rebecca C.; Simpson, Claire; Rosenberg, Avi Z.; Rosenblum, Stacy D.; Kovesdy, Csaba; Tylavsky, Frances; Myrie, Joseph; Ruiz, Bianca L.; Haque, Soulin; Mozhui, Khyobeni; Nelson, George W.; David, Victor A.; Yang, Xiaoping; Suzuki, Masako; Jacob, Jack; Reznik, Sandra E.; Kaskel, Frederick J.; Kopp, Jeffrey B.; Winkler, Cheryl A.; Davis, Robert.

In: American Journal of Human Genetics, Vol. 103, No. 3, 06.09.2018, p. 367-376.

Research output: Contribution to journalArticle

Reidy, KJ, Hjorten, RC, Simpson, C, Rosenberg, AZ, Rosenblum, SD, Kovesdy, C, Tylavsky, F, Myrie, J, Ruiz, BL, Haque, S, Mozhui, K, Nelson, GW, David, VA, Yang, X, Suzuki, M, Jacob, J, Reznik, SE, Kaskel, FJ, Kopp, JB, Winkler, CA & Davis, R 2018, 'Fetal—Not Maternal—APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry', American Journal of Human Genetics, vol. 103, no. 3, pp. 367-376. https://doi.org/10.1016/j.ajhg.2018.08.002
Reidy, Kimberly J. ; Hjorten, Rebecca C. ; Simpson, Claire ; Rosenberg, Avi Z. ; Rosenblum, Stacy D. ; Kovesdy, Csaba ; Tylavsky, Frances ; Myrie, Joseph ; Ruiz, Bianca L. ; Haque, Soulin ; Mozhui, Khyobeni ; Nelson, George W. ; David, Victor A. ; Yang, Xiaoping ; Suzuki, Masako ; Jacob, Jack ; Reznik, Sandra E. ; Kaskel, Frederick J. ; Kopp, Jeffrey B. ; Winkler, Cheryl A. ; Davis, Robert. / Fetal—Not Maternal—APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry. In: American Journal of Human Genetics. 2018 ; Vol. 103, No. 3. pp. 367-376.
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abstract = "Black Americans are at increased risk for preeclampsia. Genetic variants in apolipoprotein L1 (APOL1) account for much of the increased risk for kidney disease in blacks. APOL1 is expressed in human placenta and transgenic mice expressing APOL1 develop preeclampsia. We evaluated the role of APOL1 variants in human preeclampsia. We determined maternal and fetal APOL1 genotypes in black women with preeclampsia in two populations. At Einstein Montefiore Center (EMC) Affiliated Hospitals, we studied 121 pregnancies in black women with preeclampsia. At University of Tennessee Health Science Center (UTHSC), we studied 93 pregnancies in black women with preeclampsia and 793 pregnancies without preeclampsia. We measured serum markers of preeclampsia soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Fetal APOL1 high-risk (HR) genotype was associated with preeclampsia, with odds ratios at EMC and UTHSC of 1.84 (95{\%} CI 1.11, 2.93) and 1.92 (95{\%} CI 1.05, 3.49), respectively. Maternal APOL1 HR genotype was not associated with preeclampsia. Mothers with the fetal APOL1 HR genotype had more cerebral or visual disturbances (63{\%} versus 37{\%}, p = 0.04). In addition, fetal APOL1 HR genotype was associated with a higher sFLT-1/PlGF ratio at birth (p = 0.04). Fetal APOL1 high-risk genotype increases the risk for preeclampsia, likely by adversely affecting placental function. Further research is needed to assess whether APOL1 genetic testing can predict preeclampsia and improve pregnancy outcomes.",
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