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

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=This study compared the results of a young study group from published literature (van Rossum et al. 2004b) with those of the current study, and found no differences. Therefore, in contrast to an earlier report indicating an age-dependent enrichment for the ER22/23EK variation (van Rossum et al. 2002), no such enrichment was observed in this study. The study included several phenotypes in one cohort and a prospective analysis with a high number of deaths, including a high number of cardiovascular deaths, during the follow-up. However, the lack of data on HPA-axis reactivity or other parameters reflecting stress system activity is a weakness of the study. Nevertheless, this aspect relied on information presented in published literature. In conclusion, the results of this study show that in old age, the ER22/23EK and N363S polymorphisms but not the BclI SNP in the GR gene have an influence on metabolic profile. However, any differences in metabolic profile did not affect the prevalence of cardiovascular pathologies and the risks for all-cause and cardiovascular disease mortality at old age. 

The inclusion criteria for participants may have contributed to the results obtained. To apply similar inclusion criteria used in other studies, only independently living participants were analyzed; however, this did not change the results, nor did stratification for gender. A more likely explanation could be that some observations arose by chance, leading to false-negative or false-positive associations. Recently it has been suggested that the role of genetic variations in common traits should be built up based on evidence from many studies. Significant between-study diversity is frequent, and the results of the first study often correlate only modestly with subsequent research on the same association (Ioannidis et al. 2001).

Acknowledgements: This work was supported by an IOP grant (Innovative Oriented Research) from the Dutch Ministry of Economic Affairs (grant number IGE010114) and by the Centre for Medical Systems Biology (CMSB), which is a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NWO). The study was also supported by a Marie Curie Fellowship of the European Community programme EURO-GENDIS The Genetic Basis of Disease for Maris Kuningas, under contract number QLGA-GH-00-60005-59. Anton J. M. de Craen is thanked for help in data analyses.

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