NDT Advance Access originally published online on April 23, 2007
Nephrology Dialysis Transplantation 2007 22(9):2571-2577; doi:10.1093/ndt/gfm225
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Association between oestrogen receptor 
gene polymorphism and mortality in female end-stage renal disease patients
1Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, 2The Nephrogenetics Unit, Department of Molecular Medicine and Surgery and 3Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
Correspondence and offprint requests to: Bengt Lindholm, MD, PhD, Divisions of Renal Medicine and Baxter Novum, CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, K-56, 141 86, Stockholm, Sweden. Email: bengt.lindholm{at}ki.se
 |
Abstract |
|---|
Background. In the general population, genetic variations in the oestrogen receptor 
(ER) gene may influence lipid abnormalities, cardiovascular disease (CVD), and mortality, but this has not previously been studied in end-stage renal disease (ESRD) patients.
Methods. A total of 227 ESRD (141 men and 86 women) patients starting renal replacement therapy (RRT) were genotyped for three ER gene polymorphisms (Ser10Ser, PvuII and XbaI) and the associations between these polymorphisms and clinical and laboratory parameters and survival were analysed. Patients were followed for a median period of 55 months (range 1–126 months).
Results. The PvuII and XbaI polymorphisms were not associated with any of the clinical parameters. The ER Ser10Ser CC genotype was present in 24 (28%) of the female and in 37 (26%) of the male patients. When comparing the CC genotype with the CT and TT genotypes, there were significant differences in lipid levels and inflammatory marker levels, especially in female patients. In female patients, the CC genotype was associated with lower prevalence of protein energy wasting (PEW) (17.4% vs 43.1%; P = 0.03), lower median serum triglyceride (1.7 vs 2.1 mmol/l; P = 0.001), higher median serum albumin (34.0 vs 32.5 g/l; P = 0.03) and lower median high sensitivity-CRP (hsCRP) (2.2 vs 5.5 mg/l; P = 0.03) levels compared with the CT plus TT genotypes. In male patients only HDL-cholesterol and ApoA levels were associated with this polymorphism. Whereas this polymorphism did not influence survival in males, the mortality was lower in female patients with the CC genotype (Kaplan–Meier; Log-rank 2.2, P = 0.02). Moreover, female patients with the CT plus TT genotypes had a borderline significant increased relative risk (Cox hazard model; 6.6, 95% CI: 0.87–49.9 P = 0.06) of death as compared with those with the CC genotype, even after adjustment for age and prevalence of CVD.
Conclusions. Female, but not male ESRD patients with the ER Ser10Ser CC genotype had lower prevalence of PEW, lower serum triglyceride, higher serum albumin and lower hsCRP levels. As this genotype was associated with a significantly decreased risk of all-cause death during the initial years of RRT, its protective properties need further study.
Keywords: end-stage renal disease; oestrogen receptor ; mortality; single nucleotide polymorphisms
Received for publication: 21.12.06
Accepted in revised form: 22. 3.07