Genetic Basis of Familial Dyslipidemia and Hypertension: 15-Year Results From Utah

Abstract

The genetic and environmental determinants of hypertension, lipid abnormalities, and coronary artery disease (CAD) have been studied for 15 years in Utah in population-based multigenerational pedigrees (2500 subjects among 98 pedigrees), twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships), siblings with CAD before age 55 (45 sibships), and anecdotally ascertained pedigrees with type II diabetes (271 subjects among 16 pedigrees), lipoprotein lipase deficiency (106 subjects in a single pedigree), and familial hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong positive family history predicts a future occurrence of hypertension (relative risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found for several 'intermediate phenotypes' associated with hypertension (erythrocyte sodium-lithium countertransport, intraerythrocytic sodium, a relative fat pattern, total urinary kallikrein excretion, and fasting insulin levels). Strong single-gene effects in segregation analysis were also found for low-density lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), low high-density lipoprotein (HDL) cholesterol, and high apolipoprotein (apo) B. Deoxyribonucleic acid (DNA) markers of lipid abnormalities or hypertension have included LDL-receptor defects, lipoprotein lipase deficiency, high Lp(a), familial defective apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen, and 'glucocorticoid remediable aldosteronism (GRA) hypertension.' Also tested in Utah studies, but not found to be DNA markers for hypertension, were the genetic loci for the structural genes for renin and angiotensin-converting enzyme, and the sodium antiport system. In addition, important gene-gene interactions (LDL receptor with apo E2) and gene-environment interactions (kallikrein with potassium intake) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

A Missing Link Between a High Salt Intake and Blood Pressure Increase

“…All groups had greater urinary kallikrein activity on a low-sodium diet than on an unrestricted sodium intake, but the increase in black hypertensives was small. Segregation analysis of a large number of Utah pedigrees, covering 1.2 million subjects as well as of 140,000 Utah death certificates over a 20-year period, was carried out to elucidate the genetic environmental determinants of hypertension, lipid abnormalities, and coronary arterial diseases (50). According to that author's observation, kallikrein levels in approximately 30% of the population are low in "low homozygotes", who have a high risk of hypertension ( Fig.…”

Urinary levels of tissue kallikrein in the South African Black and Indian hypertensives

“…It is possible the American Black subjects have an abnormal gene which is affected by a low potassium intake. 27 This abnormal renal TK gene may not be present in our Black population.…”

“…Furthermore, 50% of the general population in the USA are heterozygous for the renal TK gene. 27 They are dependent upon their dietary potassium for the urinary TK excretion levels (gene-environment interaction. 27 Urinary TK has been suggested as a marker for response to hypotensive agents in Black patients.…”

“…27 They are dependent upon their dietary potassium for the urinary TK excretion levels (gene-environment interaction. 27 Urinary TK has been suggested as a marker for response to hypotensive agents in Black patients. 19 This study showed that the urinary TK levels were in general lower in Indian hypertensives compared to the Black hypertensive patients.…”

Hypertriglyceridaemia in mild hypertension: impact on cardiovascular and hormonal reactivity under different stress tests

“…The coincidence of hypertension with hyperinsulinaemia, HTG and low HDL-cholesterol represents a well known high risk group with respect to development of atheroscler-osis. 27,28 By contrast, fasting insulin, blood glucose, investigated lipid parameters and uric acid were in the same range in group C and group H.…”