Key result
SAH gene G allele is linked to higher risk of obesity, hypertension, and dyslipidemia.
Why the study?
The SAH gene was identified as a candidate gene contributing to hypertension, but its pathophysiological significance and association with metabolic risk factors were unclear.
Is the SAH gene polymorphism associated with hypertriglyceridemia, obesity, and hypertension in the general population?
Cohort (n=4,000)
Is the SAH gene polymorphism associated with hypertriglyceridemia, obesity, and hypertension in the general population?
Answers are grounded in this paper and cite their sources.
The G allele of the SAH gene is associated with a multiple-risk-factor phenotype including hypertriglyceridemia, hypercholesterolemia, 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. 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.
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Iwai et al. (2002) conducted a cohort in Hypertriglyceridemia, Obesity, and Hypertension (n=4,000). SAH gene G allele (A/G polymorphism in intron 12) vs. Non-G allele carriers / other genotypes was evaluated on Plasma triglyceride, plasma cholesterol, body mass index, waist-to-hip ratio, and blood pressure status. In a cohort of 4,000 subjects, the G allele of the SAH gene was associated with multiple risk factors, including hypertriglyceridemia, hypercholesterolemia, obesity, and hypertension.
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