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Objective: The epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension.

Methods: We investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects.

Results: The hypertension risk in individuals with interacted-genotypes (IwIw+IwIc)+(4aa), (IcIc)+(4bb+4ba) and IcIc+4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI=2.9-10.6, P<0.0001), 2.4 (95% CI=1.4-4.1, P<0.0008) and 7.5 (95% CI=1.6-34.8, P=0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (-344T/Ic)+(-922A/-786T/4a/894G) and (-344T/Ic)+(-922G/-786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI=2.0-14.2, P=0.005) and 3.9 (95% CI=1.4-10.4, P=0.04), respectively; whereas for the protective interacted-haplotypes (-344T/Iw)+(-922A/-786T/4b/894G), the odds ratio was 0.7 (95% CI=0.5-0.9, P=0.03). While the interacted-genotypes, IcIc+4aa correlated with higher SBP and MAP (P=0.006; P=0.04), the interacted-haplotypes, (-344T/Ic)+(-922A/-786T/4a/894G) and (-344T/Ic)+(-922G/-786C/4a/894G) correlated with higher MAP and lower NOx level (P=0.02 and P=0.03, respectively), and the protective interacted-haplotypes (-344T/Iw)+(-922A/-786T/4b/894G) correlated with lower PAC and MAP (P=0.024 and P=0.018, respectively).

Conclusions: The epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.

Titel:	The epistasis between vascular homeostasis genes is apparent in essential hypertension.
Autor/in / Beteiligte Person:	Kumar, R ; Nejatizadeh, A ; Gupta, M ; Markan, A ; Tyagi, S ; Jain, SK ; Pasha, MA
Zeitschrift:	Atherosclerosis, Jg. 220 (2012-02-01), Heft 2, S. 418-24
Veröffentlichung:	Limerick : Elsevier ; <i>Original Publication</i>: Amsterdam, Elsevier., 2012
Medientyp:	academicJournal
ISSN:	1879-1484 (electronic)
DOI:	10.1016/j.atherosclerosis.2011.10.036
Schlagwort:	Adult Aldosterone blood Analysis of Variance Case-Control Studies Chi-Square Distribution Female Gene Frequency Genetic Predisposition to Disease Haplotypes Humans Hypertension blood Hypertension physiopathology India Linkage Disequilibrium Male Middle Aged Nitrates blood Nitric Oxide blood Nitric Oxide Synthase Type III metabolism Nitrites blood Odds Ratio Peptidyl-Dipeptidase A genetics Peptidyl-Dipeptidase A metabolism Phenotype Risk Assessment Risk Factors Blood Pressure genetics Cytochrome P-450 CYP11B2 genetics Epistasis, Genetic Hypertension genetics Nitric Oxide Synthase Type III genetics Polymorphism, Genetic
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Atherosclerosis] 2012 Feb; Vol. 220 (2), pp. 418-24. <i>Date of Electronic Publication: </i>2011 Nov 02. MeSH Terms: Epistasis, Genetic* ; Polymorphism, Genetic* ; Blood Pressure / genetics ; Cytochrome P-450 CYP11B2 / genetics ; Hypertension / genetics ; Nitric Oxide Synthase Type III / genetics ; Adult ; Aldosterone / blood ; Analysis of Variance ; Case-Control Studies ; Chi-Square Distribution ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Hypertension / blood ; Hypertension / physiopathology ; India ; Linkage Disequilibrium ; Male ; Middle Aged ; Nitrates / blood ; Nitric Oxide / blood ; Nitric Oxide Synthase Type III / metabolism ; Nitrites / blood ; Odds Ratio ; Peptidyl-Dipeptidase A / genetics ; Peptidyl-Dipeptidase A / metabolism ; Phenotype ; Risk Assessment ; Risk Factors Substance Nomenclature: 0 (Nitrates) ; 0 (Nitrites) ; 31C4KY9ESH (Nitric Oxide) ; 4964P6T9RB (Aldosterone) ; EC 1.14.13.39 (NOS3 protein, human) ; EC 1.14.13.39 (Nitric Oxide Synthase Type III) ; EC 1.14.15.4 (Cytochrome P-450 CYP11B2) ; EC 3.4.15.1 (Peptidyl-Dipeptidase A) Entry Date(s): Date Created: 20111203 Date Completed: 20120521 Latest Revision: 20141120 Update Code: 20231215

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The epistasis between vascular homeostasis genes is apparent in essential hypertension.