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


METHODS
Large sample of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based prospective study.


METHODS
4,424 white and 3,746 black middle-aged adults.


METHODS
Genotype at the R229Q polymorphism in podocin.


RESULTS
Urinary albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) as measures of kidney damage/dysfunction.


METHODS
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.


CONCLUSIONS
Single measurement of ACR, subsample of all ARIC participants.


CONCLUSIONS
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.
Köttgen
Anna
A
Johns Hopkins University, Baltimore, MD, USA.
Hsu
Charles C
CC
Coresh
Josef
J
Shuldiner
Alan R
AR
Berthier-Schaad
Yvette
Y
Gambhir
Tejal Rami
TR
Smith
Michael W
MW
Boerwinkle
Eric
E
Kao
W H Linda
WH
D000419:Albuminuria / Q000235:genetics*; D044383:Black People; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D014481:United States; D044465:White People; D001741:Black or African American
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein