Interactive Influences of Ethnicity, Endothelin-1 Gene, and Everyday Discrimination Upon Nocturnal Ambulatory Blood Pressure

Gregoski, Mathew J.; Buxbaum, Sarah G.; Kapuku, Gaston; Dong, Yanbin; Zhu, Haidong; Davis, Mary Ellen; Gonto, Kelsey; Treiber, Frank A.

doi:10.1007/s12160-013-9472-z

Cited by 29 publications

(26 citation statements)

References 46 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%

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%

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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“…Furthermore, recent data suggest potential interactions between genetic and environmental factors-relating to the ET system-to affect cardiovascular disease, in particular 24-hour BP variability. 51 Larger studies using a selective ET A blocking strategy are needed to confirm these important findings in a group of patients at high cardiovascular risk. Main study data at baseline and week 6 of each study period.…”

Section: Perspectivesmentioning

confidence: 99%

Diurnal Variation in Blood Pressure and Arterial Stiffness in Chronic Kidney Disease

et al. 2014

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day) becomes more apparent. Importantly, loss of nocturnal dipping is associated with CKD progression.11 However, these studies did not explore interventions to restore BP dipping.Arterial stiffness also contributes significantly to the CVD risk in CKD. 12 Although some studies have examined daytime variations in arterial stiffness, none has included patients with CKD. 13,14 Furthermore, no study has as yet addressed ambulatory arterial stiffness and its 24-hour variation. Thus, there is a need for newer treatments in CKD that will not only lower BP beyond the levels achieved with standard therapies but also favorably affect the 24-hour profile of BP and arterial stiffness, leading to additional cardiovascular and renal protection.Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor produced within the vasculature. 15 ET-1 also promotes cardiovascular proliferation, inflammation, and fibrosis, all of which may contribute to poor outcomes. ET-1 is produced Abstract-Hypertension and arterial stiffness are important independent cardiovascular risk factors in chronic kidney disease (CKD) to which endothelin-1 (ET-1) contributes. Loss of nocturnal blood pressure (BP) dipping is associated with CKD progression, but there are no data on 24-hour arterial stiffness variation. We examined the 24-hour variation of BP, arterial stiffness, and the ET system in healthy volunteers and patients with CKD and the effects on these of ET receptor type A receptor antagonism (sitaxentan). There were nocturnal dips in systolic BP and diastolic BP and pulse wave velocity, our measure of arterial stiffness, in 15 controls (systolic BP, −3.2±4.8%, P<0.05; diastolic BP, −6.4±6.2%, P=0.001; pulse wave velocity, −5.8±5.2%, P<0.01) but not in 15 patients with CKD. In CKD, plasma ET-1 increased by 1.2±1.4 pg/mL from midday to midnight compared with healthy volunteers (P<0.05). Urinary ET-1 did not change. In a randomized, double-blind, 3-way crossover study in 27 patients with CKD, 6-week treatment with placebo and nifedipine did not affect nocturnal dips in systolic BP or diastolic BP between baseline and week 6, whereas dipping was increased after 6-week sitaxentan treatment (baseline versus week 6, systolic BP: −7.0±6.2 versus −11.0±7.8 mm Hg, P<0.05; diastolic BP: −6.0±3.6 versus −8.3±5.1 mm Hg, P<0.05). There was no nocturnal dip in pulse pressure at baseline in the 3 phases of the study, whereas sitaxentan was linked to the development of a nocturnal dip in pulse pressure. In CKD, activation of the ET system seems to contribute not only to raised BP but also the loss of BP dipping. The clinical significance of these findings should be explored in future clinical trials. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01770847 and NCT00810732. within the kidney and is implicated in both the development and progression of CKD. 16 The effects of ET-1 are mediated via 2 receptors, the ET A and ET B receptors, with the major pathological effects in CKD being ET A receptor mediated. 17Recen...

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“…The authors did not study specific alleles that may confer risks for elevated blood pressure, and their study raises the interesting methodological challenge of how one should interpret genetic risks that are linked to social experiences. An innovative study by Gregoski et al [51] addresses this in part by examining the relation between 24 hour ambulatory systolic blood pressure, diastolic blood pressure, nocturnal blood pressure dipping, and Everyday Discrimination among African-American and European American teens and young adults aged 16 to 20 years, who were carriers or non-carriers of the Endothelin-1/Lys198Asn T-allele, which confers an increased risk of exaggerated blood pressure reactivity to laboratory stressors. The study did not find a main effect of Everyday Discrimination on ambulatory blood pressure overall.…”

Section: Studies Of Self-reported Experiences Of Discrimination Acrosmentioning

confidence: 99%

Self-Reported Experiences of Discrimination and Cardiovascular Disease

Lewis

Williams

Tamene

et al. 2014

Curr Cardiovasc Risk Rep

135

103

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Researchers have long speculated that exposure to discrimination may increase cardiovascular disease (CVD) risk but compared to other psychosocial risk factors, large-scale epidemiologic and community based studies examining associations between reports of discrimination and CVD risk have only emerged fairly recently. This review summarizes findings from studies of self-reported experiences of discrimination and CVD risk published between 2011–2013. We document the innovative advances in recent work, the notable heterogeneity in these studies, and the considerable need for additional work with objective clinical endpoints other than blood pressure. Implications for the study of racial disparities in CVD and clinical practice are also discussed.

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Interactive Influences of Ethnicity, Endothelin-1 Gene, and Everyday Discrimination Upon Nocturnal Ambulatory Blood Pressure

Cited by 29 publications

References 46 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

Diurnal Variation in Blood Pressure and Arterial Stiffness in Chronic Kidney Disease

Self-Reported Experiences of Discrimination and Cardiovascular Disease

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