Association of genetic polymorphisms of ACADSB and COMT with human hypertension.

Abstract:

OBJECTIVES:Genetically hypertensive rats provide an excellent model to investigate the genetic mechanisms of hypertension. We previously identified three differentially expressed genes, Acadsb (short/branched chain acyl-CoA dehydrogenase), Comt (catecholamine-O-methyltransferase), and Pnpo (pyridoxine 5'-phosphate oxidase), in hypertensive and normotensive rat kidneys as potential susceptibility genes for rat hypertension. We examined the association of human homologues of these genes with human hypertension. METHODS:We sequenced three genes using samples from 48 or 96 hypertensive patients, identified single nucleotide polymorphisms, and genotyped them in a population-based sample of 1818 Japanese individuals (771 hypertensive individuals and 1047 controls). RESULTS:After adjustments for age, body mass index, present illness (hyperlipidaemia, diabetes mellitus), and lifestyle (smoking, alcohol consumption), multivariate logistic regression analysis revealed that -512A>G in ACADSB was associated with hypertension in women (AA vs AG + GG: odds ratio = 0.70, 95% confidence interval = 0.53-0.94). This single nucleotide polymorphism was in tight linkage disequilibrium with -254G>A. Furthermore, -1187G>C in COMT was associated with hypertension in men (GG vs CG + CC: odds ratio = 0.69, 95% confidence interval = 0.52-0.93) and was in tight linkage disequilibrium with 186C>T. After adjustments described above, -512 A>G and -254G>A in ACADSB were associated with variations in systolic blood pressure. ACADSB was in tight linkage disequilibrium with MGC35392 across a distance of 18.3 kb. COMT was not in linkage disequilibrium with any adjacent genes. Analysis indicated that two haplotypes of COMT were significantly associated with hypertension in men. CONCLUSION:Our study suggests the possible involvement of genetic polymorphisms in ACADSB and COMT in essential hypertension in the Japanese population.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Kamide K,Kokubo Y,Yang J,Matayoshi T,Inamoto N,Takiuchi S,Horio T,Miwa Y,Yoshii M,Tomoike H,Tanaka C,Banno M,Okuda T,Kawano Y,Miyata T

doi

10.1097/HJH.0b013e3280103a40

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

103-10

issue

1

eissn

0263-6352

issn

1473-5598

pii

00004872-200701000-00016

journal_volume

25

pub_type

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