SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study.
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.


CONCLUSIONS
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.
Telgmann
Ralph
R
Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Münster, Münster, Germany.
Brand
Eva
E
Nicaud
Viviane
V
Hagedorn
Claudia
C
Beining
Katrin
K
Schönfelder
Jacqueline
J
Brink-Spalink
Verena
V
Schmidt-Petersen
Klaus
K
Matanis
Theodoros
T
Vischer
Peter
P
Nofer
Jerzy-Roch
JR
Hasenkamp
Sandra
S
Plouin
Pierre-François
PF
Drouet
Ludovic
L
Cambien
François
F
Paul
Martin
M
Tiret
Laurence
L
Brand-Herrmann
Stefan-Martin
SM
D000328:Adult; D015992:Body Mass Index; D003066:Coenzyme A Ligases; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000150:complications / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
D011506:Proteins; C487181:ACSM3 protein, human; D003066:Coenzyme A Ligases