Polymorphisms in the Promoter Region of Catalase Gene and Essential Hypertension

Disease Markers, Jul 2018

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.

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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)


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Xiao Feng Zhou, Jing Cui, Anita L. DeStefano, Irmarie Chazaro, Lindsay A. Farrer, Athanasios J. Manolis, Haralambos Gavras, Clinton T. Baldwin. Polymorphisms in the Promoter Region of Catalase Gene and Essential Hypertension, Disease Markers, 21, DOI: 10.1155/2005/487014