Seshasai Rebecca Kurnik, Katz Ronit, de Boer Ian H, Siscovick David, Shlipak Michael G, Rifkin Dena E, Sarnak Mark J
Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA.
Clin Nephrol. 2012 Sep;78(3):174-80. doi: 10.5414/cn107427.
Previous studies suggest that the ε4 and ε2 alleles of apolipoprotein E (APOE) may be associated with decreased and increased risks of CKD, respectively, but there are limited data in older adults. We evaluated the associations of apolipoprotein E alleles with kidney function among older adults in the cardiovascular health study (CHS).
Caucasian participants had APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for longitudinal analysis). APOE variation was evaluated as an additive model with number of ε2, ε3 and ε4 alleles. GFR was estimated using the CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m2. The secondary outcome was rapid progression defined by annual loss of eGFR > 3 ml/min/1.73 m2.
Mean eGFRcreat was 72 ml/min/1.73 m2 (25% CKD). Compared with the ε3 allele, the APOE ε4 allele was associated with reduced risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval (CI) 0.79 (0.67 - 0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68 - 0.96) per allele. Results were consistent using eGFRcys. There was no association of the ε2 allele with CKD or between the apolipoprotein E gene with rapid progression.
The apolipoprotein ε4 allele was associated with lower odds of CKD in elderly Caucasian individuals. Future research should confirm these findings in other races and explore mechanisms to explain these results.
先前的研究表明,载脂蛋白E(APOE)的ε4和ε2等位基因可能分别与慢性肾脏病(CKD)风险降低和升高相关,但关于老年人的数据有限。我们在心血管健康研究(CHS)中评估了老年人中载脂蛋白E等位基因与肾功能的关联。
白种人参与者在基线时进行了APOE等位基因分析,并测量了血清肌酐和胱抑素C(横断面分析n = 3844),并在随访中进行了测量(纵向分析n = 3226)。APOE变异被评估为一个累加模型,其中包含ε2、ε3和ε4等位基因的数量。使用CKD流行病学方程(eGFRcreat)和胱抑素C人口统计学方程(eGFRcys)估算肾小球滤过率(GFR)。主要结局是由eGFR < 60 ml/min/1.73 m2定义的CKD。次要结局是由eGFR每年下降> 3 ml/min/1.73 m2定义的快速进展。
平均eGFRcreat为72 ml/min/1.73 m2(25%为CKD)。与ε3等位基因相比,APOE ε4等位基因与eGFRcreat定义的CKD风险降低相关:未调整的优势比(OR)和95%置信区间(CI)为每个等位基因0.79(0.67 - 0.93),完全调整后的OR(95% CI)为每个等位基因0.80(0.68 - 0.96)。使用eGFRcys时结果一致。ε2等位基因与CKD或载脂蛋白E基因与快速进展之间均无关联。
载脂蛋白ε4等位基因与老年白种人个体发生CKD的几率较低相关。未来的研究应在其他种族中证实这些发现,并探索解释这些结果的机制。