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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Available from: Rulan S Parekh
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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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    ABSTRACT: End-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between apoE gene polymorphisms and ESRD susceptibility. Databases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies. Sixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15-1.46, P < 0.0001; I (2) = 18%, P for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31-2.10, P < 0.0001; OR = 1.62, 95% CI 1.31-2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant. The ε2 allele of apoE gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.
    Full-text · Article · Dec 2013 · PLoS ONE
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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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    ABSTRACT: CRP gene polymorphisms are associated with serum C-reactive protein concentrations and may play a role in chronic kidney disease (CKD) progression. We recently reported an association between the gene variant rs2808630 and CKD progression in African Americans with hypertensive kidney disease. This association has not been studied in other ethnic groups. We used data from 5955 participants from Phase 2 of The Third National Health and Nutrition Examination Survey (1991-1994) to study the association between CRP polymorphisms and CKD prevalence in a population-based sample. The primary outcome was CKD defined as estimated glomerular filtration rate (eGFR) <60 ml/min or the presence of albuminuria. Secondary outcomes were the presence of albuminuria (any degree) and continuous eGFR. Six single nucleotide polymorphisms (SNPs) from the CRP gene, rs2808630, rs1205, rs3093066, rs1417938, rs3093058, and rs1800947, were evaluated. CRP rs2808630 AG compared to the referent AA genotype was associated with CKD in non-Hispanic blacks (n = 1649, 293 of whom had CKD) with an adjusted odds ratio (OR) of 3.09 (95% CI 1.65-5.8; p = 0.001). For the secondary outcomes, rs2808630 AG compared to the referent AA genotype was associated with albuminuria with an adjusted OR of 3.07 (95% CI 1.59-5.94; p = 0.002), however not with eGFR. There was no association between the SNPs and CKD, albuminuria or eGFR in non-Hispanic whites or Mexicans Americans. In this cross-sectional study, the 3' flanking CRP gene variant rs2808630 was associated with CKD, mainly through its association with albuminuria in the non-Hispanic blacks. Despite not finding an association with eGFR, our results support our previous study demonstrating an association between CRP gene variant rs2808630 and CKD progression in a longitudinal cohort of African American with hypertensive kidney disease.
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