title: A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria.
abstract: Insulin resistance characterizes type 1 diabetes in patients with albuminuria. A PC-1 glycoprotein amino acid variant, K121Q, is associated with insulin resistance. We examined the impact of the PC-1 K121Q variant on the rate of decline of the glomerular filtration rate (GFR) by creatinine clearance derived from the Cockroft-Gault formula in 77 type 1 diabetic patients with albuminuria who were followed for an average of 6.5 years (range 2.5-15). Patients carrying the Q allele (n = 22; 20 with KQ and 2 with QQ genotypes) had a faster GFR decline than those patients with the KK genotype (n = 55) (median 7.2 vs. 3.7 ml x min(-1) x year(-1); range 0.16 to 16.6 vs. -3.8 to 16.0 ml x min(-1) x year(-1); P < 0.001). Significantly more patients carrying the Q allele belonged to the highest tertile of GFR decline (odds ratio = 5.7, 95% CI 4.1-7.2, P = 0.02). Levels of blood pressure, HbA1c, and albuminuria were comparable in the two genotype groups. Albuminuria (P = 0.001), mean blood pressure (P = 0.046), and PC-1 genotype (P = 0.036) independently correlated with GFR decline. Because all patients were receiving antihypertensive treatment, the faster GFR decline in the patients carrying the Q allele could be the result of reduced sensitivity to the renoprotective effect of antihypertensive therapy. PC-1 genotyping identifies type 1 diabetic patients with a faster progression of diabetic nephropathy.
authors.affiliation: Division and Research Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. endocrinologia@operapadrepio.it
authors.forename: S
authors.initials: S
authors.lastname: De Cosmo
authors.forename: A
authors.initials: A
authors.lastname: Argiolas
authors.forename: G
authors.initials: G
authors.lastname: Miscio
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: G P
authors.initials: GP
authors.lastname: Piras
authors.forename: R
authors.initials: R
authors.lastname: Trevisan
authors.forename: P C
authors.initials: PC
authors.lastname: Perin
authors.forename: S
authors.initials: S
authors.lastname: Bacci
authors.forename: L
authors.initials: L
authors.lastname: Zucaro
authors.forename: M
authors.initials: M
authors.lastname: Margaglione
authors.forename: L
authors.initials: L
authors.lastname: Frittitta
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: V
authors.initials: V
authors.lastname: Tassi
authors.forename: G C
authors.initials: GC
authors.lastname: Viberti
authors.forename: V
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology*; D000595:Amino Acid Sequence / Q000235:genetics; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000652:urine*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D008562:Membrane Glycoproteins; D003404:Creatinine; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases