SAH gene variants revisited in the European Project On Genes in Hypertension.
OBJECTIVE
Previous studies found significant association of hypertension and hypertension-related phenotypes with genetic variation in SAH (Spontaneously hypertensive rat-clone A-Hypertension-associated). We sought independent confirmation of these findings in the European Project On Genes in Hypertension.


RESULTS
We randomly recruited 2603 relatives from 560 families and 31 unrelated subjects from six European populations (mean age 38.8 +/- 15.7 years; 52.1% women). We measured systolic/diastolic blood pressure (mean, 122.4/76.6 mmHg), body mass index (24.9 kg/m2), triceps skinfold (1.7 cm), waist-to-hip ratio (0.83 units), serum total and high-density lipoprotein (HDL) cholesterol (5.14 and 1.33 mmol/l), serum triglycerides (1.95 mmol/l) and blood glucose (4.90 mmol/l). We genotyped the G-1606A and -962del/ins polymorphisms. In all subjects, the allele frequencies were 11.8 and 29.5% for -1606A and -962del, respectively. Lewontin's D' was 0.97 (P < 0.0001). Haplotype frequencies were 58.8% for -1606G plus -962ins, 29.5% for -1606G plus -962del, and 11.7% for -1606A plus -962ins. Both before and after adjustment for covariates, none of the phenotype-genotype associations approached statistical significance. Our study had 80% power to detect on two-sided tests (P = 0.05), effect sizes of 1.8/1.3 mmHg for systolic/diastolic blood pressure, 0.52 kg/m2 for body mass index, 0.01 units for the waist-to-hip ratio, 0.96 mm for the triceps skinfold, 0.13 and 0.05 mmol/l for total and HDL cholesterol, 0.18 mmol/l for serum triglycerides, and 0.11 mmol/l for blood glucose. The family-based analyses did not reveal population stratification (P > or = 0.67).


CONCLUSIONS
The evidence supporting an association of hypertension or hypertension-related phenotypes with the SAH gene remains equivocal in human studies.
Tikhonoff
Valérie
V
Department of Clinical and Experimental Medicine, University of Padova, Italy.
Staessen
Jan A
JA
Kuznetsova
Tatiana
T
Thijs
Lutgarde
L
Hasenkamp
Sandra
S
Bäumer
Veronika
V
Stolarz
Katarzyna
K
Seidlerová
Jitka
J
Filipovský
Jan
J
Nikitin
Yuri
Y
Peleska
Jan
J
Kawecka-Jaszcz
Kalina
K
Casiglia
Edoardo
E
Brand-Herrmann
Stefan-Martin
SM
Brand
Eva
E
D000328:Adult; D001786:Blood Glucose; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D003066:Coenzyme A Ligases / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
D001786:Blood Glucose; D008074:Lipoproteins; C487181:ACSM3 protein, human; D003066:Coenzyme A Ligases