Table 3 Body composition dependent on the ER22/23EK (G/A), N363S (A/G) and BclI (C/G) polymorphisms

ER22/23EK N363S BslI C/G GG (n=507) GA/AA (n=33) P-value AA (n=497) AG/GG (n=51) P-value CC (n=236) CG/GG (n=290) P-value mean (SE) mean (SE) mean (SE) mean (SE) mean (SE) mean (SE) BMI (kg/m2) Men 26.3 (0.42) 26.1 (1.40) 0.91 26.3 (0.41) 26.0 (1.39) 0.84 25.8 (0.59) 26.6 (0.54) 0.30 Women 27.8 (0.26) 27.7 (1.15) 0.99 27.7 (0.27) 27.5 (0.80) 0.77 27.2 (0.39) 28.1 (0.35) 0.06 Weight (kg) Men 74.3 (1.22) 77.9 (4.12) 0.40 74.7 (1.19) 72.8 (4.09) 0.65 73.4 (1.72) 75.2 (1.59) 0.43 Women 67.4 (0.70) 69.6 (3.07) 0.48 67.5 (0.72) 67.2 (2.11) 0.90 66.4 (1.05) 68.2 (0.94) 0.19 Height (cm) Men 167.8 (0.50) 171.9 (1.71) 0.02 168.3 (0.50) 167.2 (1.73) 0.56 168.4 (0.69) 167.8 (0.65) 0.48 Women 156.0 (0.34) 158.6 (1.47) 0.09 156.2 (0.35) 156.6 (1.04) 0.73 156.3 (0.52) 156.1 (0.46) 0.73 Armspan (cm) Men 177.8 (0.57) 180.6 (1.97) 0.18 178.3 (0.56) 176.5 (1.93) 0.36 178.7 (0.79) 177.6 (0.74) 0.31 Women 162.4 (0.39) 164.3 (1.66) 0.26 162.5 (0.40) 162.6 (1.17) 0.91 162.5 (0.58) 162.4 (0.52) 0.85

Univariate general linear model. Data presented as means with standard errors (SE)

Table 4 Risk of cardiovascular pathologies at baseline dependent on the ER22/23EK (G/A), N363S (A/G) and BclI polymorphisms

Table 4 Risk of cardiovascular pathologies at baseline dependent on the ER22/23EK (G/A), N363S (A/G) and BclI (C/G)

ER22/23EK N363S BclI GG (n=507) GA/AA (n=33) AA (n=497) AG/GG (n=51) CC (n=236) CG /GG (n=290) infarction (n=134) 1 1.35 (0.62–2.93) 1 1.25 (0.65–2.40) 1 0.91 (0.61–1.37) ischemia (n=280) 1 1.82 (0.87–3.78) 1 1.41 (0.78–2.52) 1 0.80 (0.57–1.13) claudication (n=34) 1 0.87 (0.20–3.86) 1 1.03 (0.30–3.52) 1 1.00 (0.49–2.04) (n=56) 1 1.56 (0.58–4.24) 1 1.79 (0.79–4.05) 1 1.22 (0.69–2.16)

Sex adjusted binary logistic regression. Data presented as odds ratios (OR) with 95% confidence intervals (CI)

Discussion

another study in middle aged subjects (Lin et al. 2003), where N363S variant was associated with elevated cholesterol and triglyceride concentrations, and also with coronary artery disease. The lack of a relation between the N363S polymorphism and car- diovascular pathologies in our study population could be due to the fact that in the elderly high levels of LDL-cholesterol and triglycerides are not risk fac- tors for cardiovascular disease anymore (Weverling- Rijnsburger et al. 1997, 2003).

The aim of this study was to examine whether in old age polymorphisms in the GR gene (NR3C1) influ- ence the prevalence of cardiovascular pathologies and survival due to differences in metabolic profile and body composition. The analyses revealed differ- ences in metabolic profile for the ER22/23EK and N363S SNPs, and in body composition for the ER22/ 23EK variant, but no associations with the prevalence of cardiovascular pathologies and lifespan.

of those expected were observed. It has been previ- ously reported that elderly carriers of the ER22/23EK polymorphism have lower total cholesterol and LDL- cholesterol levels, lower fasting insulin concentra- tions, better insulin sensitivity and lower C-reactive protein levels, leading to a beneficial metabolic pro- file (van Rossum et al. 2002, 2004a). In this study, carriers of the ER22/23EK variant had higher levels of HbA1c compared to non-carriers, and a trend for higher C-reactive protein and LDL-cholesterol

Increased sensitivity to cortisol, accompanied with sub-optimal metabolic profile and increased risk for cardiovascular disease has been associated with the N363S and BclI polymorphisms (Lin et al. 2003; van Rossum et al. 2003; Di Blasio et al. 2003). In this study we found no associations with the BclI poly- morphism, but carriers of the N363S SNP had higher LDL-cholesterol and triglyceride levels, and a non- significantly higher prevalence for cardiovascular diseases. The latter results are in accordance with

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expression of less transcriptionally active GR-A protein in the ER22/23EK carriers. It was proposed that this leads to the decrease in the sensitivity to cortisol (Russcher et al. 2005). For the other two polymorphisms, N363S and BclI, the functionality has not been established in vitro. On the other hand, the polymorphisms could be functional and result in altered hormone sensitivity, which is counterbalanced by adaptive changes that attempt to normalize corti- sol signaling. These adaptive changes may vary between individuals.