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(Circulation. 2002;105:41.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Association Between SAH, an Acyl-CoA Synthetase Gene, and Hypertriglyceridemia, Obesity, and Hypertension

Naoharu Iwai, MD; Tomohiro Katsuya, MD; Toshifumi Mannami, MD; Jitsuo Higaki, MD; Toshio Ogihara, MD; Koichi Kokame, PhD; Jun Ogata, MD; Shunroku Baba, MD

From the National Cardiovascular Center (N.I., T.M., K.K., J.O., S.B.) and the Department of Geriatric Medicine, Osaka University School of Medicine (T.K., J.H., T.O.), Suita, Osaka, Japan.

Correspondence to Naoharu Iwai, MD, PhD, Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail niwai{at}res.ncvc.go.jp

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.

Methods and 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.

Key Words: lipids • obesity • hypertension • genetics

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