Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension.

Earlier studies showed association of the human SAH (Spontaneously hypertensive rat-clone A-Hypertension associated) gene with hypertension and obesity. Left ventricular mass index (LVMI) increases with blood pressure and body mass index. In a family-based population study (54.5% women; mean age, 43.1 years), we measured LVMI, mean wall thickness (MWT) and the left ventricular internal diameter (LVID) at end-diastole in 699 non-Slavic and 493 Slavic participants. In multivariable-adjusted analyses, we investigated phenotype–genotype associations (SAH G1606A and 962ins/del polymorphisms), while accounting for confounders and relatedness. Non-Slavic 1606GG homozygotes had a slightly greater LVID than 1606A allele carriers (48.6 vs. 48.0 mm; P¼0.08). However, the between-family component of the variance in LVID was significant (P¼0.005), suggesting that population stratification might explain the latter finding. Non-Slavic 962del carriers had higher LVMI (91.1 vs. 88.5 gm2; P¼0.03) and MWT (9.61 vs. 9.44 mm; P¼0.03) than 962ins homozygotes. Transmission of the 962del to non-Slavic offspring was also associated with higher MWT (P¼0.03). In Slavic participants, in the absence of population stratification (PX0.69), 1606GG homozygotes had lower LVMI (96.5 vs. 102.3 gm2; P¼0.004) and lower MWT (10.1 vs. 10.5 mm; P¼0.003) than 1606A carriers. Sensitivity analyses showed that the latter associations were confined to founders. Transmission of the 962del allele to Slavic offspring was associated with lower MWT (P¼0.007). In conclusion, LVMI and MWT, two phenotypes that are jointly influenced by blood pressure and obesity, might be related to variation in the human SAH gene.