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

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
BMC Medical Genetics (Impact Factor: 2.08). 10/2009; 10(1):108. DOI: 10.1186/1471-2350-10-108
Source: PubMed


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.
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.
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.
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.

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    • "Hsu et al. [32] proved apoE polymorphism could predict the progression of CKD independently, and increase the risk of early CKD manifestations such as high serum creatinine and macroalbuminuria. Recently, Chu et al. [33] found the ε2 allele was associated with lower levels of continuous GFR in non-Hispanic blacks. By the way, the ε2 allele in patients with type 2 diabetes is a risk factor for development of diabetic nephropathy. "
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    • "We excluded participants younger than 18 years of age (n = 979) as the modification of diet in renal disease (MDRD) equation is not applicable to them, 35 participants with missing serum creatinine concentrations, 71 participants with missing albuminuria measurements and normal kidney function, and 119 pregnant women. Our exclusion criteria were similar to other studies in general [23,24]. However we allowed participants age 18-20 years of age in the cohort, (different from other studies in the NHANES population [23,24]) as they are usually included in studies of CKD progression [25,26] and the MDRD equation applies to them. "
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