在具有全国代表性的样本中载脂蛋白E（APOE）基因多态性与慢性肾脏病的关联：第三次全国健康与营养检查调查（NHANES III）基因研究
Association of APOE polymorphism with chronic kidney disease in a nationally representative sample: a Third National Health and Nutrition Examination Survey (NHANES III) Genetic Study.
作者信息
Chu Audrey Y, Parekh Rulan S, Astor Brad C, Coresh Josef, Berthier-Schaad Yvette, Smith Michael W, Shuldiner Alan R, Kao Wen Hong L
机构信息
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
出版信息
BMC Med Genet. 2009 Oct 23;10:108. doi: 10.1186/1471-2350-10-108.
BACKGROUND
Apolipoprotein E polymorphisms (APOE) have been associated with lowered glomerular filtration rate (GFR) and chronic kidney disease (CKD) with e2 allele conferring risk and e4 providing protection. However, few data are available in non-European ethnic groups or in a population-based cohort.
METHODS
The authors analyzed 5,583 individuals from the Third National Health and Nutrition Examination Survey (NHANES III) to determine association with estimated GFR by the Modification of Diet in Renal Disease (MDRD) equation and low-GFR cases. Low-GFR cases were defined as GFR <75 ml/min/1.73 m2; additionally, GFR was analyzed continuously.
RESULTS
In univariate analysis, the e4 allele was negatively associated with low-GFR cases in non-Hispanic whites, odds ratio (OR): 0.76, 95% confidence interval (CI): 0.60, 0.97. In whites, there was a significant association between increasing APOE score (indicating greater number of e2 alleles) and higher prevalence of low-GFR cases (OR: 1.21, 95%CI: 1.01, 1.45). Analysis of continuous GFR in whites found the e4 allele was associated with higher levels of continuous GFR (beta-coefficient: 2.57 ml/min/1.73 m2, 95%CI: 0.005, 5.14); in non-Hispanic blacks the e2 allele was associated with lower levels of continuous GFR (beta-coefficient: -3.73 ml/min/1.73 m2, 95%CI: -6.61, -0.84). APOE e2 and e4 alleles were rare and not associated with low-GFR cases or continuous GFR in Mexican Americans.
CONCLUSION
In conclusion, the authors observed a weak association between the APOE e4 allele and low-GFR cases and continuous GFR in non-Hispanic whites, and the APOE e2 allele and continuous GFR in non-Hispanic blacks, but found no association with either measure of kidney function in Mexican Americans. Larger studies including multiethnic groups are needed to determine the significance of this association.
背景
载脂蛋白E基因多态性（APOE）与肾小球滤过率（GFR）降低及慢性肾脏病（CKD）相关，其中e2等位基因增加患病风险，e4等位基因则提供保护作用。然而，关于非欧洲种族群体或基于人群队列的相关数据较少。
方法
作者分析了来自第三次全国健康与营养检查调查（NHANES III）的5583名个体，以确定其与采用肾脏病饮食改良（MDRD）公式估算的GFR以及低GFR病例之间的关联。低GFR病例定义为GFR<75 ml/min/1.73 m²；此外，还对GFR进行了连续分析。
结果
在单因素分析中，e4等位基因与非西班牙裔白人中的低GFR病例呈负相关，比值比（OR）：0.76，95%置信区间（CI）：0.60，0.97。在白人中，APOE评分增加（表明e2等位基因数量更多）与低GFR病例的较高患病率之间存在显著关联（OR：1.21，95%CI：1.01，1.45）。对白人的连续GFR分析发现，e4等位基因与较高的连续GFR水平相关（β系数：2.57 ml/min/1.73 m²，95%CI：0.005，5.14）；在非西班牙裔黑人中，e2等位基因与较低的连续GFR水平相关（β系数：-3.73 ml/min/1.73 m²，95%CI：-6.61，-0.84）。APOE e2和e4等位基因在墨西哥裔美国人中罕见，且与低GFR病例或连续GFR无关。
结论
总之，作者观察到在非西班牙裔白人中，APOE e4等位基因与低GFR病例及连续GFR之间存在微弱关联，在非西班牙裔黑人中，APOE e2等位基因与连续GFR存在微弱关联，但在墨西哥裔美国人中未发现与任何一种肾功能指标存在关联。需要开展包括多种族群体的更大规模研究来确定这种关联的意义。
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