(Hypertension. 1999;33:927-932.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Different Frequencies of Inducible Nitric Oxide Synthase Genotypes in Older Hypertensives
From the Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, The University of Sydney (Australia).
Correspondence to Brian J. Morris, DSc, Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, Bldg F13, The University of Sydney, NSW 2006, Australia. E-mail brianm{at}physiol.usyd.edu.au
Abstract—A locus for essential
hypertension has been found recently on chromosome 17 in the general
vicinity of the inducible nitric oxide synthase (iNOS) gene
(NOS2A at 17cen-q11.2). We therefore tested
NOS2A markers for association and linkage with
hypertension in affected Australian Anglo-Caucasians. Patients for the
association study (n=112) were from our cohort of hypertensives
(systolic/diastolic=175±25 SD/112±19 mm Hg)
who were the offspring of 2 hypertensive parents; control subjects
(n=164) were normotensives whose parents were both normotensive. The
linkage study involved 156 hypertensive sib-pairs. Genotypes
for an 8-allele pentameric repeat located 2.6 kb upstream of
NOS2A and of a biallelic tetranucleotide
repeat 0.7 kb upstream were determined by polymerase chain reaction and
automated gene scan analysis. In the association study, the
frequency of the minor allele of the biallelic marker was 0.18 in
the hypertensives and 0.14 in the normotensives (
21 df=1.1, P=0.3). Allele
frequencies for the multiallelic marker were also similar in each group
(2 7 df=9.8, P=0.2).
Furthermore, no genotypic differences in blood pressure were apparent.
In the sib-pair study, SPLINK APM, and MAPMAKERS/SIBS did not indicate
excess allele sharing. We also examined genotype as a
function of age. In the younger (< 60 years) hypertensives as well as
younger or older normotensives, genotype and allele
frequency of the biallelic marker was similar (0.12 to 0.14). However,
in hypertensives 
60 years of age, frequency of the minor allele
was 0.28 (2=7.4, P=0.006). Homozygotes
for this allele were rare. Frequency of heterozygotes was 0.19 for
normotensives but 0.39 for the older hypertensives
(2=8.0, P=0.018) and was 0.40 for
hypertensive sibs 60 years of age with a diastolic
pressure 100 mm Hg. Furthermore, homozygotes for the major
allele were 7 years younger than heterozygotes (P=0.05
by ANOVA). In conclusion, the present study shows (1) no evidence
for a role of NOS2A in hypertension and (2) a genotypic
difference in frequency of a NOS2A promoter variant in
older hypertensives, seen in 2 different cohorts. A possible
interpretation of the latter observation is that NOS2A
genotype could affect longevity, at least in patients at high
risk by having moderate to severe hypertension.
Key Words: whites • hypertension, essential • nitric oxide synthase • genetics, biochemical • polymerase chain reaction • linkage (genetics) • survival
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