1. SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study
- Author
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Verena Brink-Spalink, Jacqueline Schönfelder, Ludovic Drouet, Stefan-Martin Brand-Herrmann, Eva Brand, Ralph Telgmann, Theodoros Matanis, Pierre-François Plouin, Sandra Hasenkamp, Claudia Hagedorn, Jerzy-Roch Nofer, Peter Vischer, Laurence Tiret, Viviane Nicaud, Katrin Beining, Martin Paul, François Cambien, and Klaus Schmidt-Petersen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,Mutation, Missense ,Gene Expression ,Single-nucleotide polymorphism ,Locus (genetics) ,Essential hypertension ,White People ,Body Mass Index ,Gene Frequency ,Internal medicine ,Coenzyme A Ligases ,Odds Ratio ,Internal Medicine ,Humans ,Medicine ,Missense mutation ,Obesity ,Allele ,Promoter Regions, Genetic ,Genetics ,Polymorphism, Genetic ,business.industry ,Haplotype ,Proteins ,Odds ratio ,Middle Aged ,medicine.disease ,Endocrinology ,Blood pressure ,Hypertension ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective The SAH gene locus has recently been proposed to be involved in obesity-related hypertension in Japanese individuals. Methods To replicate independently the initial findings in another ethnic group, we scanned the entire SAH gene in 190 Caucasian chromosomes. A total of 651 patients with essential hypertension and 776 controls (PEGASE Study) were genotyped for all identified variants using allele-specific oligonucleotides, and single nucleotide polymorphism as well as haplotype analyses were carried out. We also performed transient transfection experiments, northern and western blots, immunoprecipitation, and acyl-coenzyme A synthetase activity assays. Results We identified five polymorphisms in the promoter region (C−1808T, G−1606A, −962ins/del, G−451A, T−67C), two in introns 5 and 7 (T+9/In5C, A+20/In7T), and one missense variant (K359N). Carriage of the −1606A allele was significantly associated with hypertension [odds ratio (OR) 1.28, P = 0.049] as was 359N (OR 1.35, P = 0.048) compared with non-carriers. Conversely, for −962del, the OR for hypertension was 0.80 (P = 0.042). The SAH alleles −1606A and 359N, but not −962ins/del, displayed a raising effect on body mass index (BMI; P = 0.004 and P = 0.030, respectively) in hypertensive as well as in control individuals. After adjustment for BMI in hypertensive individuals, only the OR associated with −962ins/del remained significant (OR 0.77, P = 0.028). Functional analyses in BHK did not reveal differences for SAH 359N or 359K-containing constructs, formally excluding K359N as the functional variant. Conclusion We confirm recent evidence that the SAH locus is associated with obesity-related hypertension, in which pathophysiological context SAH variants affecting blood pressure remain, however, to be shown.
- Published
- 2007
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