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. METHODS AND 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). CONCLUSION The evidence supporting an association of hypertension or hypertension-related phenotypes with the SAH gene remains equivocal in human studies.

DOI: 10.1097/HJH.0b013e3282f2d36f


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@article{Tikhonoff2008SAHGV, title={SAH gene variants revisited in the European Project On Genes in Hypertension.}, author={Val{\'e}rie Tikhonoff and Jan A Staessen and Tatiana Kuznetsova and Lutgarde Thijs and Sandra Hasenkamp and Veronika B{\"a}umer and Katarzyna Stolarz and Jitka Ml{\'i}kov{\'a} Seidlerov{\'a} and Jan Filipovsk{\'y} and Yuri P Nikitin and Jan Peleska and Kalina Kawecka-Jaszcz and Edoardo Casiglia and Stefan-Martin Brand-Herrmann and Eva Brand}, journal={Journal of hypertension}, year={2008}, volume={26 2}, pages={244-50} }