Inherited Bimodal Traits and Susceptibility to Hypertension in Utah Pedigrees

Williams, Roger R.; Hunt, Steven C.; Hasstedt, Sandra J.; Hopkins, Paul N.; Wu, Lily; Berry, Thomas; Stults, Barry M.; Barlow, Gary K.; Kuida, Hiroshi

doi:10.1007/978-3-642-73917-0_13

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…Indeed, a method that is equivalent to the staging we describe below has been attempted for hypertension (106). Only a small percentage of the cases of hypertension can be ascribed to one of the known specific etiologies of the disease.…”

Section: Pathophysiology Of Igtmentioning

confidence: 99%

Molecular Physiology and Genetics of NIDDM: Importance of Metabolic Staging

Granner

O’Brien²

1992

Diabetes Care

126

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Insulin resistance and beta-cell failure account for the complex clinical presentation of non-insulin-dependent diabetes mellitus (NIDDM). Insulin resistance primarily involves defective regulation of hepatic glucose production and the peripheral utilization of glucose. Considerable progress has been made in understanding the basic molecular biology, biochemistry, and physiology of these processes. Similarly, the mechanisms involved in insulin synthesis, processing, storage, and secretion are being elucidated. The relative contributions of insulin resistance and beta-cell failure are difficult to evaluate when the disease is fully established and clinically apparent but may be more obvious early, i.e., in people with impaired glucose tolerance or individuals at risk for developing the disease. The latter can be identified because there is a strong genetic determinant for NIDDM; the offspring of two diabetic parents have a markedly increased incidence of the disease. In addition to genetic factors, environmental components contribute to the multifactorial etiology of NIDDM. Efforts to establish the importance of these different factors will be assisted if a metabolic staging of NIDDM can be agreed on. This staging, which should correlate the pathophysiological events responsible for the transition from normal glucose tolerance to frank NIDDM with clinical status, would be based on what is known about insulin resistance and beta-cell function. Staging will also provide for a classification of the number of causes that lead to NIDDM, if indeed, there is more than one cause of the general phenotype. Strategies for defining the gene or genes responsible for NIDDM can be subsequently devised based on the temporal sequence of appearance of pathophysiological defects and what is known about the molecular biology of insulin action. Understanding the defective metabolic code that results in NIDDM will require the concerted efforts of investigators from various disciplines. This is used throughout the text to avoid confusion with those people who have impaired glucose tolerance but not NIDDM.

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Section: Pathophysiology Of Igtmentioning

confidence: 99%

Molecular Physiology and Genetics of NIDDM: Importance of Metabolic Staging

Granner

O’Brien²

1992

Diabetes Care

126

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“…Total urinary excretion of kallikrein strongly segregates in families, and a low urinary excretion of the enzyme seems to be present as a mendelian recessive trait in 75% of the population [7,19]. Normotensives showing this trait have hypertensive first-degree relatives twice as often as those who have a high urinary excretion of kallikrein [7], These data support the hypothesis that environmental factors such as an 'inappropriate' salt intake can lead to hyperten sion in persons with some genetic abnormalities such as a low urinary excretion of kallikrein.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Salt Sensitivity on the Blood Pressure Response to Exogenous Kallikrein in Essential Hypertensive Patients

Bellini

Ferri²,

Piccoli³

et al. 1993

Nephron

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In order to verify the influence of salt sensitivity on the blood pressure response to orally administered kallikrein, we evaluated the efficacy of glandular kallikrein (derived from porcine pancreas) in 28 essential hypertensives (21 males and 9 females) aged between 40 and 62 years. After a placebo run-in period, the patients were assigned to receive oral kallikrein therapy (150 IU 3 times a day; n = 18 patients) or placebo (n = 10 patients) over a period of 8 days in a random double-blind fashion. In the salt-resistant patients (n = 8), kallikrein administration did not modify blood pressure levels. In the same group, natriuresis increased significantly after the treatment [from 94.51 ± 10.76 to Ill.65 ± 23.19 mEq/24 h (mmol/24 h), p < 0.039]. In the salt-sensitive patients (n = 10), blood pressure decreased with the kallikrein therapy (systolic: from 158.50 ± 9.20 to 144.50 ± 10.12 mm Hg, p < 0.005; diastolic: from 99.50 ± 2.16 to 90.0 ± 3.67 mm Hg, p < 0.024). In the same patients, urinary Na+ excretion increased considerably after the kallikrein treatment (from 101.07 ± 18.36 to 134.34 ± 18.27 mEq/ 24 h, p < 0.0001). Therefore, our data indicate that the oral kallikrein administration reduces blood pressure levels only in the salt-sensitive hypertensives. In both the salt-sensitive and the salt-resistant groups a marked increase in the 24-hour urinary excretion of sodium was observed after the kallikrein treatment. Therefore, the enhanced antihypertensive efficacy of the oral kallikrein administration observed in the sodium-sensitive patients is not only due to its natriuretic action but also to different kallikrein-related effects.

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“…We can hope to define several discrete gene loci and associated environmental cofactors to explain the multifactorial pathophysiology of essential hypertension. In certain individuals one or two discrete gene loci may play a predominant role (e.g., altered cellular electrolyte metabolism and sodium retention in some, 1 familial dyslipidemia and hyperinsulinemia in others. 2 In persons with a predominant genetic susceptibility, we might be able to specify the most influential environmental cofactors for prevention or treatment of that person's hypertension (e.g., sodium restriction in some, exercise and weight loss in others).…”

Section: Practical Help From Gene Markersmentioning

confidence: 99%

Will gene markers predict hypertension?

Williams

1989

Hypertension

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Inherited Bimodal Traits and Susceptibility to Hypertension in Utah Pedigrees

Cited by 8 publications

References 21 publications

Molecular Physiology and Genetics of NIDDM: Importance of Metabolic Staging

Molecular Physiology and Genetics of NIDDM: Importance of Metabolic Staging

The Influence of Salt Sensitivity on the Blood Pressure Response to Exogenous Kallikrein in Essential Hypertensive Patients

Will gene markers predict hypertension?

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