HSG/Mfn2 Gene Polymorphism and Essential Hypertension: a Case-Control Association Study in Chinese

Wang, Zuoguang; Liu, Ya; Liu, Jieling; Li, Kuo; Wen, Jin‐Kun; Wen, Shaojun; Wu, Zhaozhen

doi:10.5551/jat.5611

Cited by 19 publications

(24 citation statements)

References 24 publications

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“…39 Polymorphisms in the OPA1 and MFN2 genes are associated with hypertension. 41,42 These studies suggest links between mitochondrial dynamics and vascular disease and raise the possibility that interventions directed toward restoring normal dynamics might have therapeutic benefit.…”

Section: Mitochondrial Dynamics In Endothelial Cellsmentioning

confidence: 97%

Mitochondria and Endothelial Function

Kluge

Fetterman

Vita

2013

Circulation Research

418

365

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In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease.

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Section: Mitochondrial Dynamics In Endothelial Cellsmentioning

confidence: 97%

Mitochondria and Endothelial Function

Kluge

Fetterman

Vita

2013

Circulation Research

418

365

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“…Common variants in MFN2 have been linked to platelet count 7 and the risk of MI 25 and hypertension. 70 In addition, mutations in MFN2 have also been linked to early-onset stroke. 71 Furthermore, it is generally believed that an elevated platelet count is a risk factor for ischemic cardiovascular complications, although this has not been rigorously studied in a prospective fashion.…”

Section: Mfn2 and Human Diseasementioning

confidence: 99%

Integrative Multi-omic Analysis of Human Platelet eQTLs Reveals Alternative Start Site in Mitofusin 2

Simon

Chen

Edelstein

et al. 2016

The American Journal of Human Genetics

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Platelets play a central role in ischemic cardiovascular events. Cardiovascular disease (CVD) is a major cause of death worldwide. Numerous genome-wide association studies (GWASs) have identified loci associated with CVD risk. However, our understanding of how these variants contribute to disease is limited. Using data from the platelet RNA and expression 1 (PRAX1) study, we analyzed cis expression quantitative trait loci (eQTLs) in platelets from 154 normal human subjects. We confirmed these results in silico by performing allele-specific expression (ASE) analysis, which demonstrated that the allelic directionality of eQTLs and ASE patterns correlate significantly. Comparison of platelet eQTLs with data from the Genotype-Tissue Expression (GTEx) project revealed that a number of platelet eQTLs are platelet specific and that platelet eQTL peaks localize to the gene body at a higher rate than eQTLs from other tissues. Upon integration with data from previously published GWASs, we found that the trait-associated variant rs1474868 coincides with the eQTL peak for mitofusin 2 (MFN2). Additional experimental and computational analyses revealed that this eQTL is linked to an unannotated alternate MFN2 start site preferentially expressed in platelets. Integration of phenotype data from the PRAX1 study showed that MFN2 expression levels were significantly associated with platelet count. This study links the variant rs1474868 to a platelet-specific regulatory role for MFN2 and demonstrates the utility of integrating multi-omic data with eQTL analysis in disease-relevant tissues for interpreting GWAS results.

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“…A genetically related disease, single nucleotide polymorphisms (SNPs) of EH related genes are very important in the uncovering of nosogenesis of EH. We have found several SNPs are closely related with EH in Chinese 9. In this study, we focus on the SNP of 5'-uncoding region of Mfn2/HSG which may provide clues to the understanding of the potential mechanism of Mfn2/HSG down regulation in hypertension.…”

Section: Introductionmentioning

confidence: 99%

A Novel 5'-Uncoding Region -1248 A>G Variation of Mitofusin-2 Gene Is Associated with Hypertension in Chinese

Wang

Liu

et al. 2013

Yonsei Med J

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PurposeMitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension.Materials and Methods472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5'-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted.ResultsWhen comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was still significantly higher than in EH group (male: OR=4.264, CI 95%=2.780-6.543, p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group, either in male group or in female group. Ordinal Logistic Regression analysis showed that A>G variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01).Conclusion5'-UCR -1248 A>G variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.

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HSG/Mfn2 Gene Polymorphism and Essential Hypertension: a Case-Control Association Study in Chinese

Cited by 19 publications

References 24 publications

Mitochondria and Endothelial Function

Mitochondria and Endothelial Function

Integrative Multi-omic Analysis of Human Platelet eQTLs Reveals Alternative Start Site in Mitofusin 2

A Novel 5'-Uncoding Region -1248 A>G Variation of Mitofusin-2 Gene Is Associated with Hypertension in Chinese

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