Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah

R. R. Williams, Steven Hunt, P. N. Hopkins, L. L. Wu, S. J. Hasstedt, T. D. Berry, G. K. Barlow, B. M. Stults, M. C. Schumacher, E. H. Ludwig, S. C. Elbein, D. E. Wilson, R. P. Lifton, J. M. Lalouel

Research output: Contribution to journalArticle

78 Citations (Scopus)

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. Identification of specific sets of causal factors in many subjects with hypertension and dyslipidemia will soon be possible. Of special interest is the intersection in some families of both lipid abnormalities and hypertension involving some of these genetic and environmental factors and producing an especially high risk of early CAD.

Original languageEnglish
Pages (from-to)319-327
Number of pages9
JournalAmerican Journal of Hypertension
Volume6
Issue number11 PART 2
Publication statusPublished - Nov 1993
Externally publishedYes

Fingerprint

Dyslipidemias
Pedigree
Hypertension
Coronary Artery Disease
Apolipoproteins B
Hyperlipoproteinemia Type I
Lipids
LDL Receptors
Genes
Sodium
LDL Cholesterol
Apolipoprotein E2
Phenotype
Tissue Kallikreins
Angiotensinogen
Gene-Environment Interaction
Hyperlipoproteinemia Type II
Lipoprotein(a)
Kallikreins
Genetic Loci

Keywords

  • Blood pressure
  • cholesterol
  • epidemiology
  • genetics
  • triglycerides

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Williams, R. R., Hunt, S., Hopkins, P. N., Wu, L. L., Hasstedt, S. J., Berry, T. D., ... Lalouel, J. M. (1993). Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. American Journal of Hypertension, 6(11 PART 2), 319-327.

Genetic basis of familial dyslipidemia and hypertension : 15-year results from Utah. / Williams, R. R.; Hunt, Steven; Hopkins, P. N.; Wu, L. L.; Hasstedt, S. J.; Berry, T. D.; Barlow, G. K.; Stults, B. M.; Schumacher, M. C.; Ludwig, E. H.; Elbein, S. C.; Wilson, D. E.; Lifton, R. P.; Lalouel, J. M.

In: American Journal of Hypertension, Vol. 6, No. 11 PART 2, 11.1993, p. 319-327.

Research output: Contribution to journalArticle

Williams, RR, Hunt, S, Hopkins, PN, Wu, LL, Hasstedt, SJ, Berry, TD, Barlow, GK, Stults, BM, Schumacher, MC, Ludwig, EH, Elbein, SC, Wilson, DE, Lifton, RP & Lalouel, JM 1993, 'Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah', American Journal of Hypertension, vol. 6, no. 11 PART 2, pp. 319-327.
Williams RR, Hunt S, Hopkins PN, Wu LL, Hasstedt SJ, Berry TD et al. Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. American Journal of Hypertension. 1993 Nov;6(11 PART 2):319-327.
Williams, R. R. ; Hunt, Steven ; Hopkins, P. N. ; Wu, L. L. ; Hasstedt, S. J. ; Berry, T. D. ; Barlow, G. K. ; Stults, B. M. ; Schumacher, M. C. ; Ludwig, E. H. ; Elbein, S. C. ; Wilson, D. E. ; Lifton, R. P. ; Lalouel, J. M. / Genetic basis of familial dyslipidemia and hypertension : 15-year results from Utah. In: American Journal of Hypertension. 1993 ; Vol. 6, No. 11 PART 2. pp. 319-327.
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