title: The rs12917707 polymorphism at the UMOD locus and glomerular filtration rate in individuals with type 2 diabetes: evidence of heterogeneity across two different European populations.
abstract: BACKGROUND
  UMOD variability has been associated at a genome-wide level of statistical significance with glomerular filtration rate (GFR) in Swedish individuals with type 2 diabetes (T2D; n = 4888). Whether this finding is extensible also to diabetic patients from other populations deserves further study. Our aim was to investigate the relationship between UMOD variability and GFR in patients with T2D from Italy.
  
  
  METHODS
  Genotyping of the single nucleotide polymorphism (SNP) rs12917707 at the UMOD locus has been carried out in 3087 individuals from four independent Italian cohorts of patients with T2D by TaqMan allele discrimination.
  
  
  RESULTS
  In none of the four study cohorts was rs12917707 significantly associated with GFR (P > 0.05 for all). Similar results were obtained when the four samples were pooled and analyzed together (β = 0.83, P = 0.19). Such effect was strikingly smaller than that previously reported in Swedish patients (P for heterogeneity = 1.21 × 10-7).
  
  
  CONCLUSIONS
  The previously reported strong association between rs12917707 and GFR in diabetic patients from Sweden is not observed in Italian diabetic patients, thus clearly pointing to a heterogeneous effect across the two different samples. This suggests that UMOD is a strong genetic determinant of kidney function in patients with T2D in some, but not all, populations.
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lucchesi
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.|Department of Experimental Medicine, 'Sapienza' University, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pezzilli
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Mercuri
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Alberico
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giusti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Garofolo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.affiliation: Department of Medical Sciences, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.|Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.|Department of Experimental Medicine, 'Sapienza' University, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013548:Sweden / Q000453:epidemiology; D058949:Uromodulin / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C548612:UMOD protein, human; D058949:Uromodulin
keywords: atherosclerosis; chronic kidney disease; diabetic nephropathy; genetic susceptibility; hypertension; kidney function