Kininogen gene (KNG) variation has a consistent effect on aldosterone response to antihypertensive drug therapy: the GERA study.

TitleKininogen gene (KNG) variation has a consistent effect on aldosterone response to antihypertensive drug therapy: the GERA study.
Publication TypeJournal Article
Year of Publication2009
AuthorsBarbalic, M, Schwartz, GL, Chapman, AB, Turner, ST, Boerwinkle, E
JournalPhysiol Genomics
Volume39
Issue1
Pagination56-60
Date Published2009 Sep 09
ISSN1531-2267
KeywordsAdult, Aldosterone, Antihypertensive Agents, Female, Genetic Variation, Genotype, Humans, Kininogens, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide
Abstract

Recent experimental and clinical studies suggested that apart from playing an essential role in blood pressure homeostasis, aldosterone is involved in the pathophysiology of cardiovascular and renal diseases by inducing structural changes in the heart, kidney, and vessel wall. The interindividual variation of aldosterone response to antihypertensive treatment is considerable, and is at least partially explained by genetic variation. In this study, we investigated aldosterone response to two antihypertensive drugs-a thiazide diuretic and an angiotensin receptor blocker (ARB). Genetic variations in 50 candidate genes were tested for association with aldosterone response in four independent samples: African American (AA) responders to a diuretic (n = 289), AA responders to an ARB (n = 252), European American (EA) responders to a diuretic (n = 295) and EA responders to an ARB (n = 300). Linear regression was used to test the association with inclusion of age, sex, and body mass index as covariates. The results indicated the existence of one or more variants in the kininogen gene (KNG) that influence interindividual variation in aldosterone response. The significant association was replicated in three of four studied groups. The single nucleotide polymorphism rs4686799 was associated in AA and EA responders to the diuretic (P = 0.04 and P = 0.07, respectively), and rs5030062 and rs698078 were significantly associated in EA responders to the diuretic (P = 0.05 and P = 0.01) and EA responders to the ARB (P = 0.04 and P = 0.02). Although the clinical implication of KNG gene variation to antihypertensive drug response is yet to be determined, this novel candidate locus provides important new insights into drug response physiology.

DOI10.1152/physiolgenomics.00061.2009
Alternate JournalPhysiol. Genomics
PubMed ID19584173
PubMed Central IDPMC2747342
Grant ListR01 HL074735 / HL / NHLBI NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
HL-53335 / HL / NHLBI NIH HHS / United States
HL-74735 / HL / NHLBI NIH HHS / United States