Abstract | BACKGROUND: STUDY DESIGN: Large sample of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based prospective study. SETTING & PARTICIPANTS: 4,424 white and 3,746 black middle-aged adults. PREDICTOR: Genotype at the R229Q polymorphism in podocin. OUTCOMES: Urinary albumin- creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) as measures of kidney damage/dysfunction. MEASUREMENTS: Crude and multivariable adjusted linear and logistic regression models. RESULTS: R229Q allele frequencies were 3.7% in 4,424 white and 0.6% in 3,746 black individuals. No significant association of R229Q with increased ACR or decreased eGFR was observed (adjusted odds ratio of ACR > or = 30 mg/g in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.84; adjusted odds ratio of eGFR < 60 mL/min/1.73 m(2) in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.83). As expected, the established kidney disease risk factors hypertension and diabetes mellitus were associated strongly with measures of kidney damage/dysfunction, but the R229Q polymorphism was not associated with an additional increase in kidney disease measures. LIMITATIONS: Single measurement of ACR, subsample of all ARIC participants. CONCLUSION: No significant association of the relatively rare R229Q variant and ACR or eGFR was found in either white or black individuals. The phenotypic effect of a variant as R229Q would have to be of great magnitude to meaningfully contribute to the risk of kidney disease on a population level. The importance of such variants in the general population, as well as replication studies, can be evaluated best in large community-based studies that allow for accounting of established disease risk factors.
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Authors | Anna Köttgen, Charles C Hsu, Josef Coresh, Alan R Shuldiner, Yvette Berthier-Schaad, Tejal Rami Gambhir, Michael W Smith, Eric Boerwinkle, W H Linda Kao |
Journal | American journal of kidney diseases : the official journal of the National Kidney Foundation
(Am J Kidney Dis)
Vol. 52
Issue 5
Pg. 868-75
(Nov 2008)
ISSN: 1523-6838 [Electronic] United States |
PMID | 18499321
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- NPHS2 protein
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Topics |
- Albuminuria
(genetics)
- Black People
- Female
- Glomerular Filtration Rate
- Humans
- Intracellular Signaling Peptides and Proteins
(genetics)
- Male
- Membrane Proteins
(genetics)
- Middle Aged
- Polymorphism, Genetic
- Prospective Studies
- United States
- White People
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