title: The association of podocin R229Q polymorphism with increased albuminuria or reduced estimated GFR in a large population-based sample of US adults.
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.
  
  
  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.
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hsu
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Yvette
authors.initials: Y
authors.lastname: Berthier-Schaad
authors.forename: Tejal Rami
authors.initials: TR
authors.lastname: Gambhir
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: 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
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein