Polymorphisms in the Promoter Region of Catalase Gene and Essential Hypertension
Disease Markers
0278-0240
Polymorphisms in the promoter region of catalase gene and essential hypertension
Xiao Feng Zhou 0
Jing Cui 1
Anita L. DeStefano 3 4
Irmarie Chazaro 1 4
Lindsay A. Farrer 2 3 5
Athanasios J. Manolisg
Haralambos Gavras 1
Clinton T. Baldwin 0
0 Center for Human Genetics, Department of Medicine, Boston University School of Medicine , Boston, MA , USA
1 Hypertension Section, Boston University School of Medicine , Boston, MA , USA
2 Genetics Program, Boston University School of Medicine , Boston, MA , USA
3 Department of Neurology, Boston University School of Medicine , Boston, MA , USA
4 Department of Biostatistics, Boston University School of Public Health , Boston, MA , USA
5 Department of Epidemiology, Boston University School of Public Health , Boston, MA , USA
Genetic variations that predispose individuals to complex disorders, such as essential hypertension, may be found in gene coding regions, intronic regions or in gene promoter regions. Most studies have focused on gene variations that result in amino acid substitutions because they result in different isoforms of the protein, presumably resulting in differences in protein properties. Less attention has been placed on the role of intronic or promoter mutations. In this report, we examined two single nucleotide polymorphisms (SNPs) in the catalase (CAT) gene prompter region in a cohort of hypertensive Caucasians and African Americans with a Mass Spec based Homogenous MassEXTEND assay. We found an association when a specific combination of the two promoter SNPs was examined in Caucasians. No association was observed in African Americans. Our data suggest that genetic variations in the promoter region of catalase gene influence the susceptibility to essential hypertension. In addition, the genetic factors that contribute to hypertension maybe different between ethnic groups.
Catalase; essential hypertension; SNP; promoter
1. Introduction
Essential hypertension is an idiopathic elevation of
blood pressure. It affects approximately 24% of the
adult population in US [
1
] and is a recognized risk
factor for cardiovascular, cerebrovascular and renal
disease. Although the etiology of essential hypertension
is unknown, it involves the interaction between
heritable and environmental factors. The major
neurohumoral mechanisms involved in systemic blood
pressure regulation and hypertensive complications are well
understood and include the renin-angiotensin
aldosterone system [
2
], the sympathoadrenal system [
3
], the
kallikrein-kinin system [
4
] and others. There are also
numerous enzymes such as catalase [
5
] affecting the
metabolism of local tissue protective or damaging
factors [
6
], which have been described to contribute to
blood pressure dysregulation. The genes for these
enzymes are likely candidates for molecular genetic
analysis, because their variants may predispose individuals
to hypertension.
Numerous studies have demonstrated association
between hypertension and polymorphisms of genes such
as angiotensin converting enzyme [
7
],
angiotensinogen [
8,9
], beta2-adrenergic receptor [10], and
alphaadducin [
11,12
] in some hypertensive populations.
Fewer reports have examined the association between
promoter mutations and hypertension. Two single
nucleotide polymorphisms (SNPs) have been reported in
the Catalase gene (CAT), one (CAT-844) being
associated with higher blood pressure among a group of
Chinese hypertensives [13] and the second (CAT-262)
showing association with catalase activity levels in a
Swedish population [
14
]. Catalase regulates the plasma
level of reactive oxygen species [
5
] and together with
nitric oxide (NO), it influences angiotensin converting
enzyme activation, LDL oxidation, adhesion molecule
expression, platelet aggregation, endothelial cell
apoptosis, and vascular smooth cell growth [
6
].
In this report, we examined these CAT SNPs in a
collection of hypertensive Caucasians and African
Americans and ethnically matched normotensive controls and
found an association with hypertension. Our results
suggest that promoter mutations in CAT gene may
contribute to the development of essential hypertension.
2. Materials and methods
2.1. Study population
African American patients with essential
hypertension were identified from several clinics at the Boston
Medical Center, Boston MA USA. Caucasian patients
were identified at Tzanion Hospital, Piraeus Greece.
All subjects provided informed consent and human
subject review boards at both institutions approved this
study. Individuals were classified as hypertensive if
pretreatment systolic blood pressure was 140 mm Hg,
pretreatment diastolic blood pressure was 90 mm Hg,
or the individual was being treated for hypertension. A
routine clinical evaluation was carried out and,
whenever clinically appropriate, additional standard
diagnostic procedures were conducted to exclude organic
causes of secondary hypertension (eg, renovasc (...truncated)