Association between oestrogen receptor α gene polymorphism and mortality in female end-stage renal disease patients

Sawako Kato, Bengt Lindholm, Jonas Axelsson, Rashid A. Qureshi, Peter Barany, Olof Heimbürger, Jan Åke Gustafsson, Peter Stenvinkel, Louise Nordfors

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background. In the general population, genetic variations in the oestrogen receptor α (ERα) 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 ERα 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 ERα 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 ERα 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.

Original languageEnglish (US)
Pages (from-to)2571-2577
Number of pages7
JournalNephrology Dialysis Transplantation
Volume22
Issue number9
DOIs
StatePublished - Sep 2007

Keywords

  • End-stage renal disease
  • Mortality
  • Oestrogen receptor α
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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