title: SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation.
abstract: Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FEcreat) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with (125)I-iothalamate clearance. Creatinine clearance was also assessed. FEcreat was calculated from the simultaneous clearances of creatinine and (125)I-iothalamate. Donor rs316009 was associated with FEcreat (beta -0.053, P = 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16-1.67], P = 0.00065, and 1.23 [1.02-1.48], P = 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD.
authors: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. a.reznichenko@umcg.nl
authors: Anna
authors: A
authors: Reznichenko
authors: Steef J
authors: SJ
authors: Sinkeler
authors: Harold
authors: H
authors: Snieder
authors: Jacob
authors: J
authors: van den Born
authors: Martin H
authors: MH
authors: de Borst
authors: Jeffrey
authors: J
authors: Damman
authors: Marcory C R F
authors: MC
authors: van Dijk
authors: Harry
authors: H
authors: van Goor
authors: Bouke G
authors: BG
authors: Hepkema
authors: Jan-Luuk
authors: JL
authors: Hillebrands
authors: Henri G D
authors: HG
authors: Leuvenink
authors: Jan
authors: J
authors: Niesing
authors: Stephan J L
authors: SJ
authors: Bakker
authors: Marc
authors: M
authors: Seelen
authors: Gerjan
authors: G
authors: Navis
mesh_terms: D000328:Adult; D003404:Creatinine / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D000075102:Organic Cation Transporter 2
chemical_list: D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D003404:Creatinine