Dataset Information

Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.

ABSTRACT:

Background

The epoxyeicosatrienoic acids (EETs) have antihypertensive, anti-inflammatory, and organ protective properties and their circulation levels are related to hypertension, diabetes mellitus, cardiovascular diseases, and preeclampsia. Soluble epoxide hydrolase (sEH) catalyses the degradation of EETs to less biologically active dihydroxyeicosatrienoic acids. Here, we sequenced the promoter region of EPHX2 to investigate the association between promoter sequence alterations that we thought to affect the expression levels of the enzyme and preeclampsia (PE).

Methods

Nucleotide sequencing of the promoter region of the EPHX2, spanning from position -671 to +30, was performed on 100 pregnant women with PE and, 20 or more weeks pregnant normotensive, healthy women (n=100).

Results

Pregnant women who carry rs4149235, rs4149232, rs73227309, and rs62504268 polymorphisms have 4.4, 2.4, 2.3, and 2.8 times significantly increased risk of PE, respectively. CCGG (OR: 3.11; 95% CI: 1.12-8.62) and CCCA (OR: 0.45; 95% CI: 0.36-0.55) haplotypes were associated with an increased and decreased risk of PE, respectively.

Conclusions

Four SNPs (rs4149232, rs4149235, rs73227309, and rs62504268) in the promoter region of the EPHX2, and CCGG and CCCA haplotypes of these 4 SNPs were significantly associated with PE. These SNPs in the promoter region may affect sEH expression and thus enzyme activity and may play a role in PE pathogenesis by causing individual differences in EET levels. However, future studies are needed to confirm our findings and examine the effect of these SNPs on the sEH expression and/or enzyme activity.

SUBMITTER: Sar? I

PROVIDER: S-EPMC7710375 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.

Sarı İsmail İ Ökten Hatice H Aktan Çağdaş Ç Cihan Esra E

Journal of medical biochemistry 20201001 4

<h4>Background</h4>The epoxyeicosatrienoic acids (EETs) have antihypertensive, anti-inflammatory, and organ protective properties and their circulation levels are related to hypertension, diabetes mellitus, cardiovascular diseases, and preeclampsia. Soluble epoxide hydrolase (sEH) catalyses the degradation of EETs to less biologically active dihydroxyeicosatrienoic acids. Here, we sequenced the promoter region of <i>EPHX2</i> to investigate the association between promoter sequence alterations t ...[more]

PMID: 33312058

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Project description:BACKGROUND:Preeclampsia is a serious pregnancy-specific syndrome with incompletely understood pathogenesis. Previous study has demonstrated that the decreased CXCR2 in preeclamptic placentas may contribute to the development of preeclampsia. The role of single nucleotide polymorphisms (SNPs) of CXCR2 gene in the pathogenesis of preeclampsia remains largely unexplored. Thus, we aimed to investigate the association between polymorphisms of CXCR2 gene and preeclampsia in Han Chinese women. METHODS:Totally 481 pregnant women, including 243 controls and 238 patients with preeclampsia were recruited. The rs1126579 and rs2230054 polymorphisms in CXCR2 gene were tested using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:Significantly increased risk of preeclampsia was observed in the rs1126579 CC or TC/CC genotypes when compared with TT genotype (CC vs. TT: odss ratio [OR] = 2.11, 95% confidence interval [CI] = 1.18-3.76, p = 0.039; TC/CC vs. TT: OR = 1.89, 95% CI = 1.29-2.78, p = 0.001). Markedly higher risk of preeclampsia was found to be associated with rs1126579 TC genotype (TC vs. TT/CC: OR = 1.48, 95% CI = 1.04-2.12, p = 0.031). After stratification analysis, the different distribution of TC/CC genotypes was particularly significant in the severe preeclampsia group (OR = 2.15, 95% CI = 1.42-3.24, p < 0.01), the early-onset severe preeclampsia group (OR = 1.97, 95% CI = 1.14-3.42, p = 0.013), and the late-onset severe preeclampsia group (OR = 2.29, 95% CI = 1.39-3.78, p < 0.01). Besides, TC genotype carriers had a 1.55 fold increased risk of severe preeclampsia (95% CI = 1.06-2.27, p = 0.022) and a 1.80 fold increased risk of late onset severe preeclampsia (95% CI = 1.14-2.83, p = 0.01) than those of TT/CC genotype carriers. CONCLUSIONS:Our study suggests a genetic association between rs1126579 polymorphism in CXCR2 gene and increased risk of preeclampsia. These data provide a new clue for future investigation.

Project description:Preeclampsia is a complex genetic disorder and its pathogenesis remains to be investigated. Single nucleotide polymorphisms serve important roles in genetic predisposition. The present study aimed to explore the association between runt-related transcription factor 3 (RUNX3) gene polymorphisms in severe preeclampsia (SPE) and clinical features.A total of 417 participants were enrolled in the present study. The rs2236852, rs7528484 and rs760805 polymorphisms of the RUNX3 gene were tested using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Clinical information of patients and controls was collected. Relationship between clinical feature and different genotype was analyzed.Compared with rs2236852 GG genotype carriers, the odds ratios (OR) for the risk of SPE were 2.26 [95% confidence interval (CI), 1.24-4.12; P = .023] in AA genotype carriers. A significantly increased risk of SPE was associated with AG/AA genotypes compared with GG genotypes (OR, 1.74; 95% CI, 1.11-2.75; P = .015). AA homozygote carriers with SPE exhibited lower birth weight, shorter birth length and reduced incidence of hypoproteinemia compared with AG heterozygote carriers (P <.05). A significantly increased risk of SPE was determined to be associated with the rs7528484 CC genotype in codominant and recessive models (CC vs TT: OR, 3.70, 95% CI, 1.31-10.43, P = .01; CC vs TT/TC: OR, 3.98, 95% CI, 1.46-10.87, P = .003). Patients carrying C-allele (TC + CC) presented increased systolic pressure and an increased incidence of neonatal pneumonia compared with TT homozygote carriers (P <.05). Compared with rs760805 TT homozygote carriers, patients carrying AA homozygote exhibited significantly reduced 24 hours urinary protein levels, lower serum creatinine concentrations and a decreased incidence of neonatal asphyxia (P <.05).The present study suggested a genetic association between RUNX3 gene polymorphisms and SPE. The data provided a novel insight to guide future investigations.

Dataset Information

Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.

Background

Methods

Results

Conclusions

Publications

Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.

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