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The association of podocin R229Q polymorphism with increased albuminuria or reduced estimated GFR in a large population-based sample of US adults.

TitleThe association of podocin R229Q polymorphism with increased albuminuria or reduced estimated GFR in a large population-based sample of US adults.
Publication TypeJournal Article
Year of Publication2008
AuthorsKöttgen A, Hsu CC, Coresh J, Shuldiner AR, Berthier-Schaad Y, Gambhir TRami, Smith MW, Boerwinkle E, Kao LWH
JournalAm J Kidney Dis
Volume52
Issue5
Pagination868-75
Date Published2008 Nov
ISSN1523-6838
KeywordsAfrican Continental Ancestry Group, Albuminuria, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Middle Aged, Polymorphism, Genetic, Prospective Studies, United States
Abstract

BACKGROUND: Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis. The objective of this study is to assess the contribution of the commonly reported functional podocin polymorphism R229Q to kidney disease in the population at large and replicate a prior study of an association of R229Q and albuminuria in the general population.

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

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.

DOI10.1053/j.ajkd.2008.02.306
Alternate JournalAm J Kidney Dis
PubMed ID18499321
PubMed Central IDPMC2597304
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
R21 DK073482-02 / DK / NIDDK NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R21 DK073482 / DK / NIDDK NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
K01-DK-067207 / DK / NIDDK NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States