Association between oestrogen receptor alpha gene polymorphism and mortality in female end-stage renal disease patients.
BACKGROUND
In the general population, genetic variations in the oestrogen receptor alpha (ERalpha) 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 ERalpha 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 ERalpha 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 ERalpha 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.
Kato
Sawako
S
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, K-56, 141 86, Stockholm, Sweden.
Lindholm
Bengt
B
Axelsson
Jonas
J
Qureshi
Rashid A
RA
Barany
Peter
P
Heimbürger
Olof
O
Gustafsson
Jan-Ake
JA
Stenvinkel
Peter
P
Nordfors
Louise
L
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017582:Renal Replacement Therapy
D047628:Estrogen Receptor alpha