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-nucleotid...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.830446/full |
| _version_ | 1818231977823698944 |
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| author | Shudan Wei Xiangyuan Yu Xiaolan Wen Min Zhang Qi Lang Ping Zhong Bo Huang |
| author_facet | Shudan Wei Xiangyuan Yu Xiaolan Wen Min Zhang Qi Lang Ping Zhong Bo Huang |
| author_sort | Shudan Wei |
| collection | DOAJ |
| 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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| last_indexed | 2024-12-12T10:58:58Z |
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| spelling | doaj.art-135ff682ef694714837e1908423f01ea2022-12-22T00:26:34ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.830446830446Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control StudyShudan Wei0Xiangyuan Yu1Xiaolan Wen2Min Zhang3Qi Lang4Ping Zhong5Bo Huang6Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Guilin Medical University, Guilin, ChinaGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.830446/fullhypertensive disorders of pregnancymetallothioneinsingle-nucleotide polymorphismcase-control studygenetic susceptibility |
| spellingShingle | Shudan Wei Xiangyuan Yu Xiaolan Wen Min Zhang Qi Lang Ping Zhong Bo Huang Genetic Variations in Metallothionein Genes and Susceptibility to Hypertensive Disorders of Pregnancy: A Case-Control Study Frontiers in Genetics hypertensive disorders of pregnancy metallothionein single-nucleotide polymorphism case-control study genetic susceptibility |
| 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 | hypertensive disorders of pregnancy metallothionein single-nucleotide polymorphism case-control study genetic susceptibility |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.830446/full |
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