Hypertension Clinical Trial
To determine whether low total urinary kallikrein activity was prospectively associated with new hypertension onset or elevated blood pressures.
BACKGROUND:
Statistical evidence had been found for a dominant major gene segregating in large pedigrees
for high urinary kallikrein levels protecting against hypertension which explained 51
percent of the variance of total urinary kallikrein (TUK). In normotensive adult and
pediatric pedigree members, low urinary kallikrein activity was associated with a positive
family history of hypertension, stroke, and/or coronary disease.
DESIGN NARRATIVE:
The presence of a previously reported dominant major gene inferred from segregation analysis
of total urinary kallikrein activity (TUK) in selected pedigrees was verified on already
collected frozen urine specimens. Subjects were rescreened to obtain measured nine year
follow-up blood pressure data. Individuals were classified by assigned baseline TUK genotype
and tested to determine whether low TUK was prospectively associated with new hypertension
onset or elevated blood pressures. Because a major gene effect was implicated, available
probes for the structural kallikrein gene or other related products regulating kallikrein
were tested for genetic linkage to TUK levels. Correlations with over 600 variables measured
at baseline in pedigrees and twins were tested to analyze the strong familiality of
environment, refine the genetic analyses to better assign genotypes, and detect
gene-environment interactions. All baseline variables except kallikrein, aldosterone, and
prostaglandin measurements on frozen urine and follow-up blood pressure had already been
collected.
TUK may be a marker for a renal, cellular or other physiological abnormality influencing
both TUK expression and susceptibility to hypertension. Therefore, the relationship of TUK
to urinary aldosterone, prostaglandin E excretion and already measured urinary electrolytes,
plasma renin activity, and baseline and reactive blood pressures was determined. Genetic
segregation analyses were performed of the urinary variables and other variables closely
associated with TUK.
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N/A
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