Kato Sawako, Lindholm Bengt, Axelsson Jonas, Qureshi Rashid A, Barany Peter, Heimbürger Olof, Gustafsson Jan-Ake, Stenvinkel Peter, Nordfors Louise
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, K-56, 141 86, Stockholm, Sweden.
Nephrol Dial Transplant. 2007 Sep;22(9):2571-7. doi: 10.1093/ndt/gfm225. Epub 2007 Apr 23.
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.
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).
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.
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.
在普通人群中，雌激素受体α（ERα）基因的遗传变异可能影响脂质异常、心血管疾病（CVD）和死亡率，但此前尚未在终末期肾病（ESRD）患者中进行过研究。
对227例开始肾脏替代治疗（RRT）的ESRD患者（141例男性和86例女性）进行了三种ERα基因多态性（Ser10Ser、PvuII和XbaI）的基因分型，并分析了这些多态性与临床和实验室参数及生存率之间的关联。患者随访中位时间为55个月（范围1 - 126个月）。
PvuII和XbaI多态性与任何临床参数均无关联。ERα Ser10Ser CC基因型在24例（28%）女性患者和37例（26%）男性患者中存在。将CC基因型与CT和TT基因型进行比较时，脂质水平和炎症标志物水平存在显著差异，尤其是在女性患者中。在女性患者中，CC基因型与蛋白质能量消耗（PEW）患病率较低相关（17.4%对43.1%；P = 0.03），血清甘油三酯中位数较低（1.7对2.1 mmol/l；P = 0.001），血清白蛋白中位数较高（34.0对32.5 g/l；P = 0.03），高敏C反应蛋白（hsCRP）中位数较低（2.2对5.5 mg/l；P = 0.03），与CT加TT基因型相比。在男性患者中，只有高密度脂蛋白胆固醇和载脂蛋白A水平与这种多态性相关。虽然这种多态性不影响男性的生存率，但CC基因型的女性患者死亡率较低（Kaplan - Meier；对数秩检验2.2，P = 0.02）。此外，即使在调整年龄和CVD患病率后，CT加TT基因型的女性患者与CC基因型的女性患者相比，死亡相对风险仍有临界显著增加（Cox风险模型；6.6，95%可信区间：0.87 - 49.9，P = 0.06）。
具有ERα Ser10Ser CC基因型的女性ESRD患者，而非男性，PEW患病率较低，血清甘油三酯较低，血清白蛋白较高，hsCRP水平较低。由于这种基因型与RRT最初几年全因死亡风险显著降低相关，其保护特性需要进一步研究。
