The impact of G5665T polymorphism of endothelin-1 gene, on endothelin-1 levels and left ventricular function in ischemic heart disease

Tousoulis, Dimitris; Toli, Eirini; Miliou, Antigoni; Papageorgiou, Nikolaos S.; Antoniades, Charalambos; Kampoli, Anna–Maria; Hatzis, George; Kormali, Labrini; Metaxa, Sofia; Papaoikonomou, Stavroula; Tsiamis, Eleftherios; Stefanadis, Christodoulos

doi:10.1016/j.ijcard.2013.01.188

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…This is the first time an association between endothelin-1 (G5665T) gene polymorphism and sickle cell disease has been established. Association between this gene and other disease syndromes is widely established with its homozygous variant contributing to disease outcome or severity 31–35. The present observation demands extensive genome-wide analysis in different population groups, particularly other African and African American sickle cell groups, considering the phenotypic similarity and genotypic heterogeneity in the latter.…”

Section: Discussionmentioning

confidence: 97%

“…Association between this gene and other disease syndromes is widely established with its homozygous variant contributing to disease outcome or severity. [31][32][33][34][35] The present observation demands extensive genome-wide analysis in different population groups, particularly other African and African American sickle cell groups, considering the phenotypic similarity and genotypic heterogeneity in the latter. The observation of geographic-structured alignment in genetic markers among African Americans is consistent with underlying genetic differences in geographic variation for disease susceptibility [36][37][38][39][40][41] and how this relates to sickle cell pathogenesis makes for an interesting conclusion.…”

Section: Discussionmentioning

confidence: 99%

“…To genotype the G5665T (rs5370) polymorphism on the endothelin-1 (ET-1) gene, a revised version of a previously published PCR protocol 35 and an PCR-RFLP assay was employed. Primer pairs rs5370F: 5′-TCTTGCTTTATTAGGTCGGAGACC-3′ and rs5370R: 5′-TTTGAACGAGGACGCTGGTC-3′ was used to amplify a part of the gene, with PCR setup and amplification conditions as follows: 95 °C for 10 min, and 35 cycles of 95 °C for 1 min (denaturation), 61 °C for 1 min (annealing), 72 °C for 1 min and 30 s (extension) and 72 °C for 10 min (final extension).…”

Section: Methodsmentioning

confidence: 99%

“…endothelin-1 (G5665T) polymorphism. To genotype the G5665T (rs5370) polymorphism on the endothelin-1 (ET-1) gene, a revised version of a previously published PCR protocol 35 rs5370F: 5′-TCTTGCTTTATTAGGTCGGAGACC-3′ and rs5370R: 5′-TTTGAACGAGGACGCTGGTC-3′ was used to amplify a part of the gene, with PCR setup and amplification conditions as follows: 95 °C for 10 min, and 35 cycles of 95 °C for 1 min (denaturation), 61 °C for 1 min (annealing), 72 °C for 1 min and 30 s (extension) and 72 °C for 10 min (final extension). PCR products of 262 bp were digested with 2U Cac8I (New England Biolabs, Boston MA) restriction endonuclease (2 hour incubation) at 37 °C on an Eppendorf gradient Mastercycler.…”

Section: Genotyping Of the Variable Number Of Tandem Repeats (Vntr) Pmentioning

confidence: 99%

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Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa

Thakur

Guindo

Cullifer

et al. 2014

Gene�Regul Syst Bio

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Sickle cell disease shows marked variability in severity and pathophysiology among individuals, probably linked to differential expression of various adhesion molecules. In this study, we investigated the differential distribution, genomic diversity and haplotype frequency of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) polymorphisms, recently implicated as important in modification of disease severity. One hundred and forty five sickle cell disease patients (HbSS) and 244 adult and pediatric controls, without sickle cell disease (HbAA), were recruited from Mali. Genotypic analysis of the functionally significant eNOS variants (T786C, G894T and intron 4) and endothelin-1 (G5665T) was carried out with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our results show that the wild type alleles are the most frequent for all eNOS variants between cases and controls. Allelic and genotypic frequencies of eNOS polymorphic groups are not significantly different between cases and controls (P > 0.05). In addition, there is no association between eNOS variants and sickle cell disease, contrary to published reports. On the other hand, we report that endothelin-1 (G5665T) mutant variant had the lowest allelic frequency, and is significantly associated with sickle cell disease in Africa (P < 0.05). Similarly, haplotype frequencies were the same between cases and controls, except for the haplotype combining all mutant variants (T, C, 4a; P = 0.01). eNOS polymorphic variants are less frequent, with no significance with sickle cell disease in Africa. On the other hand, endothelin-1 is associated with sickle cell disease, and has the capacity to redefine pathophysiology and possibly serve as modulator of disease phenotype.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Genotyping Of the Variable Number Of Tandem Repeats (Vntr) Pmentioning

confidence: 99%

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Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa

Thakur

Guindo

Cullifer

et al. 2014

Gene�Regul Syst Bio

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“…PCR genotyping for all three endothelial nitric oxide synthase (a polymorphism in the promoter region T786C, rs2070744; another in exon 7 Glu298Asp, rs1799983; and the variable number of tandem repeats in intron 4) and endothelin-1 (G5665T) polymorphisms were carried out as published. 19 , 20 , 22 Amplified PCR products were digested with specific restriction enzymes, as shown previously, while fragment size analysis was carried out as reported. 19 , 20 , 23 …”

Section: Methodsmentioning

confidence: 99%

Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology

et al. 2016

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Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331) and control (n = 379) groups, with a polymerase–chain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12) and allelic frequencies (p = 2.20E-16) between groups. The most common haplotype is the combination of T786C homozygote wild-type variant with homozygote mutant variants of G5665T (ET-1) and Glu298Asp (eNOS). These results show that endothelin-1 (rs5370) polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.

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Endothelin and the heart in health and diseases

Miyauchi

Sakai

2019

Peptides

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The impact of G5665T polymorphism of endothelin-1 gene, on endothelin-1 levels and left ventricular function in ischemic heart disease

Cited by 4 publications

References 10 publications

Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa

Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa

Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology

Endothelin and the heart in health and diseases

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