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HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy

Racial disparity exists for hypertensive disorders in pregnancy (HDP), which leads to disparate morbidity and mortality worldwide. The enzyme heme oxygenase-1 (HO-1) is encoded by HMOX1, which has genetic polymorphisms in its regulatory region that impact its expression and activity and have been as...

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Autores principales: Sun, Tianyanxin, Cruz, Giovanna I., Mousavi, Nima, Marić, Ivana, Brewer, Alina, Wong, Ronald J., Aghaeepour, Nima, Sayed, Nazish, Wu, Joseph C., Stevenson, David K., Leonard, Stephanie A., Gymrek, Melissa, Winn, Virginia D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734242/
https://www.ncbi.nlm.nih.gov/pubmed/35697922
http://dx.doi.org/10.1007/s43032-022-01001-1
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author Sun, Tianyanxin
Cruz, Giovanna I.
Mousavi, Nima
Marić, Ivana
Brewer, Alina
Wong, Ronald J.
Aghaeepour, Nima
Sayed, Nazish
Wu, Joseph C.
Stevenson, David K.
Leonard, Stephanie A.
Gymrek, Melissa
Winn, Virginia D.
author_facet Sun, Tianyanxin
Cruz, Giovanna I.
Mousavi, Nima
Marić, Ivana
Brewer, Alina
Wong, Ronald J.
Aghaeepour, Nima
Sayed, Nazish
Wu, Joseph C.
Stevenson, David K.
Leonard, Stephanie A.
Gymrek, Melissa
Winn, Virginia D.
author_sort Sun, Tianyanxin
collection PubMed
description Racial disparity exists for hypertensive disorders in pregnancy (HDP), which leads to disparate morbidity and mortality worldwide. The enzyme heme oxygenase-1 (HO-1) is encoded by HMOX1, which has genetic polymorphisms in its regulatory region that impact its expression and activity and have been associated with various diseases. However, studies of these genetic variants in HDP have been limited. The objective of this study was to examine HMOX1 as a potential genetic contributor of ancestral disparity seen in HDP. First, the 1000 Genomes Project (1 KG) phase 3 was utilized to compare the frequencies of alleles, genotypes, and estimated haplotypes of guanidine thymidine repeats (GTn; containing rs3074372) and A/T SNP (rs2071746) among females from five ancestral populations (Africa, the Americas, Europe, East Asia, and South Asia, N = 1271). Then, using genomic DNA from women with a history of HDP, we explored the possibility of HMOX1 variants predisposing women to HDP (N = 178) compared with an equivalent ancestral group from 1 KG (N = 263). Both HMOX1 variants were distributed differently across ancestries, with African women having a distinct distribution and an overall higher prevalence of the variants previously associated with lower HO-1 expression. The two HMOX1 variants display linkage disequilibrium in all but the African group, and within EUR cohort, LL and AA individuals have a higher prevalence in HDP. HMOX1 variants demonstrate ancestral differences that may contribute to racial disparity in HDP. Understanding maternal genetic contribution to HDP will help improve prediction and facilitate personalized approaches to care for HDP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43032-022-01001-1.
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spelling pubmed-97342422022-12-11 HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy Sun, Tianyanxin Cruz, Giovanna I. Mousavi, Nima Marić, Ivana Brewer, Alina Wong, Ronald J. Aghaeepour, Nima Sayed, Nazish Wu, Joseph C. Stevenson, David K. Leonard, Stephanie A. Gymrek, Melissa Winn, Virginia D. Reprod Sci Maternal Fetal Medicine/Biology: Original Article Racial disparity exists for hypertensive disorders in pregnancy (HDP), which leads to disparate morbidity and mortality worldwide. The enzyme heme oxygenase-1 (HO-1) is encoded by HMOX1, which has genetic polymorphisms in its regulatory region that impact its expression and activity and have been associated with various diseases. However, studies of these genetic variants in HDP have been limited. The objective of this study was to examine HMOX1 as a potential genetic contributor of ancestral disparity seen in HDP. First, the 1000 Genomes Project (1 KG) phase 3 was utilized to compare the frequencies of alleles, genotypes, and estimated haplotypes of guanidine thymidine repeats (GTn; containing rs3074372) and A/T SNP (rs2071746) among females from five ancestral populations (Africa, the Americas, Europe, East Asia, and South Asia, N = 1271). Then, using genomic DNA from women with a history of HDP, we explored the possibility of HMOX1 variants predisposing women to HDP (N = 178) compared with an equivalent ancestral group from 1 KG (N = 263). Both HMOX1 variants were distributed differently across ancestries, with African women having a distinct distribution and an overall higher prevalence of the variants previously associated with lower HO-1 expression. The two HMOX1 variants display linkage disequilibrium in all but the African group, and within EUR cohort, LL and AA individuals have a higher prevalence in HDP. HMOX1 variants demonstrate ancestral differences that may contribute to racial disparity in HDP. Understanding maternal genetic contribution to HDP will help improve prediction and facilitate personalized approaches to care for HDP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43032-022-01001-1. Springer International Publishing 2022-06-13 /pmc/articles/PMC9734242/ /pubmed/35697922 http://dx.doi.org/10.1007/s43032-022-01001-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Maternal Fetal Medicine/Biology: Original Article
Sun, Tianyanxin
Cruz, Giovanna I.
Mousavi, Nima
Marić, Ivana
Brewer, Alina
Wong, Ronald J.
Aghaeepour, Nima
Sayed, Nazish
Wu, Joseph C.
Stevenson, David K.
Leonard, Stephanie A.
Gymrek, Melissa
Winn, Virginia D.
HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title_full HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title_fullStr HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title_full_unstemmed HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title_short HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy
title_sort hmox1 genetic polymorphisms display ancestral diversity and may be linked to hypertensive disorders in pregnancy
topic Maternal Fetal Medicine/Biology: Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734242/
https://www.ncbi.nlm.nih.gov/pubmed/35697922
http://dx.doi.org/10.1007/s43032-022-01001-1
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