Association of Epoxide Hydrolase 2 Gene Arg287Gln with the Risk for Primary Hypertension in Chinese

Ma, Liang; Zhao, Hailing; Yu, Meijie; Wen, Yunfei; Zhao, Tingting; Yan, Meihua; Liu, Qian; Jiang, Yongwei; Cao, Yongtong; Li, Ping; Niu, Wenquan

doi:10.1155/2020/2351547

Cited by 8 publications

(9 citation statements)

References 27 publications

(26 reference statements)

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“…Alzheimer's disease [11], hypertension [12] and familial hypercholesterolemia [13]. In contrast, most studies of EPHX2 in cancer have thus far been limited to speci c tumor types and there has been no report on the association studies between EPHX2 and pan-cancer.…”

Section: Introductionmentioning

confidence: 99%

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

Zhao

et al. 2022

Preprint

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Background Accumulating evidence indicates the essential role of EPHX2 in tumorigenesis. However, to date, no studies have performed a systematic evaluation of EPHX2 gene in human cancers and the predictive role of EPHX2 in cancer immunotherapy response has still not been explored. Methods In the present study, Oncomine, TIMER2, UALCAN, GEPIA2, PrognoScan, HPA and Kaplan-Meier Plotter database were utilized to comprehensively analyze the expression landscape and prognostic clinical value of EPHX2 across 33 human cancers. To gain a better understanding of the role of EPHX2 in cancer immunotherapy, the correlations between EPHX2 and tumor immune microenvironment (TME) such as immune cell infiltrations, immune modulators, and the major histocompatibility complex were demonstrated. The underlying EPHX2-associated signaling pathways in cancer were also analysed. Moreover, the correlation between EPHX2 and immunotherapeutic biomarkers such as tumor mutational burden (TMB) and microsatellite instability (MSI) was explored. At last, the potential immune checkpoint blockers (ICB) response was predicted using tumor immune dysfunction and exclusion (TIDE) algorithm. Results Overall, the mRNA expression of EPHX2 was significantly downregulated in the majority of tumors compared with normal tissues. Despite the significant prognostic value of EPHX2 expression across cancers, EPHX2 played a protective or detrimental role in different kinds of cancers. Generally speaking, immune cell infiltrations, immune modulators and immunotherapeutic biomarkers were all strongly related to the expression of EPHX2. Besides, EPHX2 expression was significantly related to immune-relevant pathways, especially in PAAD, THYM and UVM. Furthermore, our study demonstrated diverse response patterns of ICB in response to EPHX2 expression in different tumor types. Conclusion Our findings here suggest that EPHX2 could be a prognostic factor in multiple cancers and play an important role in tumor immunity by affecting infiltrating immune cells, TMB and MSI. This study provides further insight into the role of EPHX2 in tumor immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

Zhao

et al. 2022

Preprint

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“…Genetic variants of the epoxide hydrolase (EPHX2) gene were associated with the development of HTN and CVDs. 10,12 The presence of the EPHX2 rs41507953 variant within Caucasians was reported to be a risk factor in coronary heart disease. 13 In addition, it was reported that EPHX2 rs41507953 variant can increase the risk of HTN and ischaemic strokes in Sweden males.…”

Section: Introductionmentioning

confidence: 99%

“…Genetic variants of the epoxide hydrolase ( EPHX2 ) gene were associated with the development of HTN and CVDs 10,12 . The presence of the EPHX2 rs41507953 variant within Caucasians was reported to be a risk factor in coronary heart disease 13 .…”

Section: Introductionmentioning

confidence: 99%

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No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients

Khamees

Jarrar

Al-Qirim

et al. 2021

Int. J. Clin. Pract.

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Background: Human soluble epoxide hydrolase plays a major role in cardiovascular homoeostasis. Genetic variants in the EPHX2 gene among different ethnic groups are associated with cardiovascular complications, such as hypertension. However, no reports regarding the association of EPHX2 genotype with hypertension among type II diabetic (T2D) patients of Middle Eastern Jordanian origin exist.Objective: The current study aimed to elucidate the association of the EPHX2 allele, genotype and haplotype with T2D, hypertension and parameters of lipid profile parameters among Jordanian T2D patients.Methods: Ninety-three genomic DNA samples of non-diabetic controls and 97 samples from T2D patients were genotyped for EPHX2 rs4149243, rs2234914 and rs751142 genetic variants. The DNA samples were amplified using polymerase chain reaction (PCR) and then sequenced using Applied Biosystems Model (ABI3730x1).The functionality of intronic EPHX2 variants was predicted using the in silico Berkely Drosophila Genome Project software.Results: We found no significant (P >.05) association between the EPHX2 rs4149243, rs2234914 and rs751142 allele, genotype and haplotype and the incidence of T2D and hypertension. Additionally, no association (P >.05) between these EPHX2 genetic variants with the baseline total cholesterol, low-and high-density lipoproteins and triglycerides among both non-diabetic and diabetic volunteers was found. However, we found an inter-ethnic variation (χ 2 -test, P value ˂ .05) in the allele frequency of the EPHX2 rs4149243 and rs2234914 variants between Jordanians and other ethnic populations. Also, the in silico Berkely Drosophila Genome Project software predicted that the intronic EPHX2 rs4149243 could alter the splicing of intron 7.Conclusions: It can be concluded from this study that EPHX2 rs4149243, rs2234914 and rs751142 genetic variants do not play a role in the development of T2D and hypertension among Jordanian T2D patients. Further genetic studies with larger sample sizes are needed to find out the association of other functional EPHX2 variants with cardiovascular diseases among T2D patients in Jordan. How to cite this article: Khamees M, Jarrar Y, Al-Qirim T, et al. No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients. Int J Clin Pract.

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“…EPHX2 encodes soluble epoxide hydrolase (sEH) [4], which is an important enzyme in the degradation of endogenous lipid epoxide, especially the inactivation of epoxyeicosatrienoic acids (EETs) [5]. Dysregulation of EPHX2 contributes to the pathogenesis of several diseases, such as prostate, liver and kidney cancers[6-8], atherosclerosis [9], Parkinson's disease [10], Alzheimer's disease [11], hypertension [12] and familial hypercholesterolemia [13]. In contrast, most studies of EPHX2 in cancer have thus far been limited to speci c tumor types and there has been no report on the association studies between EPHX2 and pan-cancer.…”

Section: Introductionmentioning

confidence: 99%

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

Zhao

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Accumulating evidence indicates the essential role of EPHX2 in tumorigenesis. However, to date, no studies have performed a systematic evaluation of EPHX2 gene in human cancers and the predictive role of EPHX2 in cancer immunotherapy response has still not been explored. Methods: In the present study, Oncomine, TIMER2, UALCAN, GEPIA2, PrognoScan, HPA and Kaplan-Meier Plotter database were utilized to comprehensively analyze the expression landscape and prognostic clinical value of EPHX2 across 33 human cancers. To gain a better understanding of the role of EPHX2 in cancer immunotherapy, the correlations between EPHX2 and tumor immune microenvironment (TME) such as immune cell infiltrations, immune modulators, and the major histocompatibility complex were demonstrated. The underlying EPHX2-associated signaling pathways in cancer were also analysed. Moreover, the correlation between EPHX2 and immunotherapeutic biomarkers such as tumor mutational burden (TMB) and microsatellite instability (MSI) was explored. At last, the potential immune checkpoint blockers (ICB) response was predicted using tumor immune dysfunction and exclusion (TIDE) algorithm. Results: Overall, the mRNA expression of EPHX2 was significantly downregulated in the majority of tumors compared with normal tissues. Despite the significant prognostic value of EPHX2 expression across cancers, EPHX2 played a protective or detrimental role in different kinds of cancers. Generally speaking, immune cell infiltrations, immune modulators and immunotherapeutic biomarkers were all strongly related to the expression of EPHX2. Besides, EPHX2 expression was significantly related to immune-relevant pathways, especially in PAAD, THYM and UVM. Furthermore, our study demonstrated diverse response patterns of ICB in response to EPHX2 expression in different tumor types. Conclusion: Our findings here suggest that EPHX2 could be a prognostic factor in multiple cancers and play an important role in tumor immunity by affecting infiltrating immune cells, TMB and MSI. This study provides further insight into the role of EPHX2 in tumor immunotherapy.

show abstract

Association of Epoxide Hydrolase 2 Gene Arg287Gln with the Risk for Primary Hypertension in Chinese

Cited by 8 publications

References 27 publications

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients

Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

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