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


CONCLUSIONS
Our study suggests the possible involvement of genetic polymorphisms in ACADSB and COMT in essential hypertension in the Japanese population.
Kamide
Kei
K
Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka, Japan. kamide@hsp.ncvc.go.jp
Kokubo
Yoshihiro
Y
Yang
Jing
J
Matayoshi
Tetsutaro
T
Inamoto
Nozomu
N
Takiuchi
Shin
S
Horio
Takeshi
T
Miwa
Yoshikazu
Y
Yoshii
Masayoshi
M
Tomoike
Hitonobu
H
Tanaka
Chihiro
C
Banno
Mariko
M
Okuda
Tomohiko
T
Kawano
Yuhei
Y
Miyata
Toshiyuki
T
D044944:Acyl-CoA Dehydrogenases / Q000235:genetics*; D000225:Adenine; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D015331:Cohort Studies; D003596:Cytosine; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006147:Guanine; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D051740:Ikaros Transcription Factor; D007564:Japan; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011734:Pyridoxaminephosphate Oxidase / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics; D017678:Sex Distribution; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; C418108:IKZF5 protein, human; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D006147:Guanine; D003596:Cytosine; D044944:Acyl-CoA Dehydrogenases; D011734:Pyridoxaminephosphate Oxidase; D008780:Methyltransferases; D000225:Adenine