Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension.
BACKGROUND
The SA gene (SAH) has been isolated by differential screening from a genetically hypertensive rat strain as a candidate gene that may contribute to hypertension. Recently, the SA protein has been reported to be highly homologous to bovine xenobiotic-metabolizing medium-chain fatty acid:CoA ligase.


RESULTS
To clarify the pathophysiological significance of SAH, we searched for polymorphisms of human SAH and performed association studies using a large cohort (4000 subjects) representing the general population in Japan. We found 2 polymorphisms in the promoter region and single-nucleotide polymorphisms in introns 5, 7, and 12 and exon 8. One of the variants, an A/G polymorphism in intron 12, just 7 bp upstream from exon 13, strongly affected plasma triglyceride, plasma cholesterol, body mass index (BMI), waist-to-hip ratio (W/H), and blood pressure status. The effect of this genotype on blood pressure seems to be conveyed through its effects on BMI and W/H. Transient expression of the SA protein in mammalian cells confirmed that it is expressed in mitochondria and has medium-chain fatty acid:CoA ligase activity. The A/G polymorphism was found to be associated with the expression level of SA mRNA in peripheral mononuclear cells in vivo.


CONCLUSIONS
The G allele of SAH was found to be associated with multiple risk factors, including hypertriglyceridemia, hypercholesterolemia, obesity, and hypertension. This observation should open a new area for future research in multiple-risk-factor syndromes.
Iwai
Naoharu
N
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. niwai@res.ncvc.go.jp
Katsuya
Tomohiro
T
Mannami
Toshifumi
T
Higaki
Jitsuo
J
Ogihara
Toshio
T
Kokame
Koichi
K
Ogata
Jun
J
Baba
Shunroku
S
D000483:Alleles; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D019556:COS Cells; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D004247:DNA; D003066:Coenzyme A Ligases