Current knowledge regarding the genetics of human hypertension.
Observations over 11 years from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are reviewed to illustrate research approaches, developing results and prospects for future studies. Strong associations with hypertension have been found for several biochemical tests that show substantial genetic determination. Suggestions of recessive major gene effects and significant polygenic background determinations have been found for several variables, including urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport and sodium-potassium cotransport. Each of these variables is related in some way to sodium or potassium metabolism, or both, and may help to improve the understanding of a possibly inherited susceptibility to hypertension that is related to dietary electrolyte intake. A second major group of factors involving familial predisposition to hypertension include lipid abnormalities (increased very-low- and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol); increased fasting insulin levels or insulin resistance, or both; obesity (especially central or upper body obesity); and multiple environmental factors influencing these metabolic systems, including dietary fat, carbohydrate and calorie intake; physical exercise; and certain antihypertensive medications that adversely affect lipid metabolism and glucose tolerance. Some studies even suggest a possible link between these two large groups of factors (electrolyte metabolism and lipid-insulin metabolism). Hypertriglyceridaemia and hyperinsulinaemia are both significantly correlated with increased levels of several cation-flux tests. It is recommended that studies of human hypertension apply these biochemical profiles to study sibships with two or more hypertensive siblings as a cost-effective initial approach.(ABSTRACT TRUNCATED AT 250 WORDS)
Williams
R R
RR
University of Utah, Cardiovascular Genetics Research Clinic, Salt Lake City 84108.
Hunt
S C
SC
Hasstedt
S J
SJ
Hopkins
P N
PN
Wu
L W
LW
Berry
T D
TD
Stults
B M
BM
Barlow
G K
GK
Schumacher
M C
MC
Kuida
H
H
D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D004573:Electrolytes; D007328:Insulin