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

Audrey Y. Chu, Rulan S. Parekh, Brad C. Astor, Josef Coresh, Yvette Berthier-Schaad, Michael W. Smith, Alan R. Shuldiner, Wen H L Kao

Research output: Contribution to journalArticle

Abstract

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 2; 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 (β-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 (β-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.

Original languageEnglish (US)
Article number1471
Pages (from-to)108
Number of pages1
JournalBMC Medical Genetics
Volume10
DOIs
StatePublished - Oct 23 2009

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Nutrition Surveys
Apolipoproteins E
Glomerular Filtration Rate
Chronic Renal Insufficiency
Alleles
Confidence Intervals
Odds Ratio
Diet Therapy
Kidney
Ethnic Groups

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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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. / Chu, Audrey Y.; Parekh, Rulan S.; Astor, Brad C.; Coresh, Josef; Berthier-Schaad, Yvette; Smith, Michael W.; Shuldiner, Alan R.; Kao, Wen H L.

In: BMC Medical Genetics, Vol. 10, 1471, 23.10.2009, p. 108.

Research output: Contribution to journalArticle

Chu, Audrey Y. ; Parekh, Rulan S. ; Astor, Brad C. ; Coresh, Josef ; Berthier-Schaad, Yvette ; Smith, Michael W. ; Shuldiner, Alan R. ; Kao, Wen H L. / 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. In: BMC Medical Genetics. 2009 ; Vol. 10. pp. 108.
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abstract = "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 2; 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 (β-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 (β-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.",
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T2 - A Third National Health and Nutrition Examination Survey (NHANES III) Genetic Study

AU - Chu, Audrey Y.

AU - Parekh, Rulan S.

AU - Astor, Brad C.

AU - Coresh, Josef

AU - Berthier-Schaad, Yvette

AU - Smith, Michael W.

AU - Shuldiner, Alan R.

AU - Kao, Wen H L

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Y1 - 2009/10/23

N2 - 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 2; 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 (β-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 (β-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.

AB - 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 2; 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 (β-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 (β-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.

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