Aims/hypothesis: About 35% of individuals with type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for microvascular complications like diabetic nephropathy. Recent genome-wide association studies have identified the uromodulin locus (UMOD), encoding the most common protein in human urine to be associated with hypertension and also with chronic kidney disease (CKD). In the present study we examined the association of the common variant of the uromodulin (UMOD) gene with type 2 diabetic nephropathy and kidney function.
Methods: UMOD variant rs13333226 was genotyped in a case–control material including 4888 unrelated type 2 diabetic individuals (n = 880 with and n = 4008 without nephropathy) from Sweden (Scania Diabetes Registry) using the ABI Real time TaqMan allelic discrimination assay.
Results: The G allele of rs13333226 was associated with a decreased risk of nephropathy [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69–0.91, P = 0.001] after correction for confounding factors like age, sex, body mass index (BMI), blood pressure, kidney function, smoking and duration of diabetes. The same allele was also associated with a better kidney function [estimated glomerular filtration rate (eGFR), β = 0.117, P < 0.0001] and lower systolic blood pressure (β = −0.048, P = 0.013) in the overall study cohort.
Conclusion/interpretation: The present study highlights that the common variant of the UMOD gene is protective against diabetic nephropathy susceptibility and also affects kidney function and blood pressure in patients with type 2 diabetes. However, the association with diabetic nephropathy was independent of blood pressure and kidney function.
aDepartment of Endocrinology and Lund University Diabetes Centre
bDepartment of Clinical Sciences, University Hospital, Skane, Malmo, Sweden
Correspondence to Tarunveer S. Ahluwalia, PhD, Department of Clinical Sciences – Diabetes and Endocrinology, Lund University Diabetes Centre, Entrance 72, Building 91, Plan 12, Clinical Research Centre (CRC), University Hospital Skane (UMAS), 20502 Malmo, SwedenTel: +46 40 391211; fax: +46 40 391222; e-mail: Tarun.Ahluwalia@med.lu.se
Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; GWAS, genome-wide association studies; SNP, singlenucleotide polymorphism; THP, TammHorsfall protein; UMOD, uromodulin
Received 4 April, 2011
Revised 7 June, 2011
Accepted 14 June, 2011