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Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study

Background: The involvement of oxidative stress in the pathological process of hypertensive disorders of pregnancy (HDP) gives rise to the interest in exploring the association of genetic variations in antioxidant metallothionein (MT) genes with HDP susceptibility. Methods: Seventeen single-nucleoti...

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Autores principales: Wei, Shudan, Yu, Xiangyuan, Wen, Xiaolan, Zhang, Min, Lang, Qi, Zhong, Ping, Huang, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208279/
https://www.ncbi.nlm.nih.gov/pubmed/35734434
http://dx.doi.org/10.3389/fgene.2022.830446
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author Wei, Shudan
Yu, Xiangyuan
Wen, Xiaolan
Zhang, Min
Lang, Qi
Zhong, Ping
Huang, Bo
author_facet Wei, Shudan
Yu, Xiangyuan
Wen, Xiaolan
Zhang, Min
Lang, Qi
Zhong, Ping
Huang, Bo
author_sort Wei, Shudan
collection PubMed
description Background: The involvement of oxidative stress in the pathological process of hypertensive disorders of pregnancy (HDP) gives rise to the interest in exploring the association of genetic variations in antioxidant metallothionein (MT) genes with HDP susceptibility. Methods: Seventeen single-nucleotide polymorphisms(SNPs) in MT genes were selected to conduct genotyping based on a case-control study consisting of 371 HDP cases (pregnancy with chronic hypertension (66), gestational hypertension (172), and preeclampsia or preeclampsia superimposed on chronic hypertension (133)) and 479 controls. The association between SNPs in MTs and the risk of HDP was estimated with unconditional logistic regression analysis and further tested with the false-positive report probability (FPRP) procedure. The joint effects of SNPs on the HDP risk were assessed by haplotype analysis. Results: After the adjustment for age and pre-pregnancy body mass index (pre-BMI) in the logistic regress analysis and followed by the FPRP test, the genetic variation rs10636 (OR = 0.46, 95% CI: 0.30–0.71 for GG vs. CC, p = 0.000 and OR = 0.48, 95% CI: 0.32–0.73 for GG vs. CG/CC, p = 0.001) in MT2A was associated with gestational hypertension. Other four SNPs, that is, rs11076161 (OR = 1.89, 95% CI: 1.35–2.63 for GG vs. GA/AA, p = 0.000) in MT1A; rs7191779 (OR = 1.54, 95% CI: 1.11–2.13 for CC vs. CG/GG, p = 0.010) in MT1B; rs8044719 (OR = 0.57, 95% CI: 0.40–0.80 for GT vs. GG, p = 0.001) in MT1DP; and rs8052334 (OR = 1.52, 95% CI: 1.10–2.11 for TT vs. TC/CC, p = 0.012) in MT1B were significantly associated with the susceptibility of HDP. The haplotype analysis among 11, 10, 10, and seven SNPs in MT (MT1A, MT2A, MT1M, MT1B, and MT1DP) genes showed that eight (A-C-G-T-C-G-A-G-C-G-C, OR = 4.559; A-C-T-C-C-C-A-G-C-G-C, OR = 5.777; A-C-T-T-C-G-A-G-C-G-C, OR = 4.590; G-A-T-C-C-G-C-G-G-C-C, OR = 4.065; G-A-T-C-G-C-C-G-G-C-C, OR = 4.652; G-A-T-T-C-C-C-G-G-C-C, OR = 0.404; G-C-T-C-C-C-A-G-G-C-C, OR = 1.901; G-C-T-T-C-C-A-G-G-C-C, and OR = 3.810), five (C-G-A-T-C-A-C-C-G-G, OR = 2.032; C-G-A-T-C-G-C-C-G-G, OR = 2.077; G-A-C-T-C-A-C-C-T-G, OR = 0.564; G-G-A-G-C-A-C-C-G-G, OR = 5.466; G-G-A-T-T-A-G-C-G-G, and OR = 0.284), five (A-C-G-T-C-G-A-G-C-C, OR = 2.399; A-C-T-C-C-C-C-T-G-G, OR = 0.259; G-A-T-C-C-C-C-G-G-C, OR = 1.572; G-A-T-C-G-C-C-G-G-C, OR = 0.001; G-C-T-C-G-C-A-G-G-C, and OR = 2.512), and five (A-C-T-C-C-C-G, OR = 0.634; G-A-G-C-C-C-G, OR = 4.047; G-A-T-T-G-C-G, OR = 0.499; G-C-G-T-C-A-G, and OR = 7.299; G-C-T-C-C-A-G, OR = 1.434) haplotypes were significantly associated with pregnancy with chronic hypertension, gestational hypertension, preeclampsia, or preeclampsia superimposed on chronic hypertension and HDP. Conclusion: These variant MT alleles and their combination patterns may be used as genetic markers for predicting HDP susceptibility.
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spelling pubmed-92082792022-06-21 Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study Wei, Shudan Yu, Xiangyuan Wen, Xiaolan Zhang, Min Lang, Qi Zhong, Ping Huang, Bo Front Genet Genetics Background: The involvement of oxidative stress in the pathological process of hypertensive disorders of pregnancy (HDP) gives rise to the interest in exploring the association of genetic variations in antioxidant metallothionein (MT) genes with HDP susceptibility. Methods: Seventeen single-nucleotide polymorphisms(SNPs) in MT genes were selected to conduct genotyping based on a case-control study consisting of 371 HDP cases (pregnancy with chronic hypertension (66), gestational hypertension (172), and preeclampsia or preeclampsia superimposed on chronic hypertension (133)) and 479 controls. The association between SNPs in MTs and the risk of HDP was estimated with unconditional logistic regression analysis and further tested with the false-positive report probability (FPRP) procedure. The joint effects of SNPs on the HDP risk were assessed by haplotype analysis. Results: After the adjustment for age and pre-pregnancy body mass index (pre-BMI) in the logistic regress analysis and followed by the FPRP test, the genetic variation rs10636 (OR = 0.46, 95% CI: 0.30–0.71 for GG vs. CC, p = 0.000 and OR = 0.48, 95% CI: 0.32–0.73 for GG vs. CG/CC, p = 0.001) in MT2A was associated with gestational hypertension. Other four SNPs, that is, rs11076161 (OR = 1.89, 95% CI: 1.35–2.63 for GG vs. GA/AA, p = 0.000) in MT1A; rs7191779 (OR = 1.54, 95% CI: 1.11–2.13 for CC vs. CG/GG, p = 0.010) in MT1B; rs8044719 (OR = 0.57, 95% CI: 0.40–0.80 for GT vs. GG, p = 0.001) in MT1DP; and rs8052334 (OR = 1.52, 95% CI: 1.10–2.11 for TT vs. TC/CC, p = 0.012) in MT1B were significantly associated with the susceptibility of HDP. The haplotype analysis among 11, 10, 10, and seven SNPs in MT (MT1A, MT2A, MT1M, MT1B, and MT1DP) genes showed that eight (A-C-G-T-C-G-A-G-C-G-C, OR = 4.559; A-C-T-C-C-C-A-G-C-G-C, OR = 5.777; A-C-T-T-C-G-A-G-C-G-C, OR = 4.590; G-A-T-C-C-G-C-G-G-C-C, OR = 4.065; G-A-T-C-G-C-C-G-G-C-C, OR = 4.652; G-A-T-T-C-C-C-G-G-C-C, OR = 0.404; G-C-T-C-C-C-A-G-G-C-C, OR = 1.901; G-C-T-T-C-C-A-G-G-C-C, and OR = 3.810), five (C-G-A-T-C-A-C-C-G-G, OR = 2.032; C-G-A-T-C-G-C-C-G-G, OR = 2.077; G-A-C-T-C-A-C-C-T-G, OR = 0.564; G-G-A-G-C-A-C-C-G-G, OR = 5.466; G-G-A-T-T-A-G-C-G-G, and OR = 0.284), five (A-C-G-T-C-G-A-G-C-C, OR = 2.399; A-C-T-C-C-C-C-T-G-G, OR = 0.259; G-A-T-C-C-C-C-G-G-C, OR = 1.572; G-A-T-C-G-C-C-G-G-C, OR = 0.001; G-C-T-C-G-C-A-G-G-C, and OR = 2.512), and five (A-C-T-C-C-C-G, OR = 0.634; G-A-G-C-C-C-G, OR = 4.047; G-A-T-T-G-C-G, OR = 0.499; G-C-G-T-C-A-G, and OR = 7.299; G-C-T-C-C-A-G, OR = 1.434) haplotypes were significantly associated with pregnancy with chronic hypertension, gestational hypertension, preeclampsia, or preeclampsia superimposed on chronic hypertension and HDP. Conclusion: These variant MT alleles and their combination patterns may be used as genetic markers for predicting HDP susceptibility. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9208279/ /pubmed/35734434 http://dx.doi.org/10.3389/fgene.2022.830446 Text en Copyright © 2022 Wei, Yu, Wen, Zhang, Lang, Zhong and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wei, Shudan
Yu, Xiangyuan
Wen, Xiaolan
Zhang, Min
Lang, Qi
Zhong, Ping
Huang, Bo
Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title_full Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title_fullStr Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title_full_unstemmed Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title_short Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study
title_sort genetic variations in metallothionein genes and susceptibility to hypertensive disorders of pregnancy: a case-control study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208279/
https://www.ncbi.nlm.nih.gov/pubmed/35734434
http://dx.doi.org/10.3389/fgene.2022.830446
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