A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria

• Published in: Diabetes (New York, N.Y.) Vol. 49; no. 3; pp. 521 - 524
• Main Authors: De Cosmo, S, Argiolas, A, Miscio, G, Thomas, S, Piras, G P, Trevisan, R, Perin, P C, Bacci, S, Zucaro, L, Margaglione, M, Frittitta, L, Pizzuti, A, Tassi, V, Viberti, G C, Trischitta, V
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.03.2000
• Subjects: Adult; Albuminuria - etiology; Amino Acid Sequence - genetics; Cohort Studies; Creatinine; Creatinine - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - urine; Diabetic Nephropathies - genetics; Diabetic Nephropathies - physiopathology; Disease Progression; Female; Genetic Variation; Genotype; Glomerular Filtration Rate; Humans; Insulin resistance; Male; Measurement; Membrane Glycoproteins - genetics; Phosphoric Diester Hydrolases; Physiological aspects; Pyrophosphatases; Retrospective Studies; Time Factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.49.3.521

A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria. S De Cosmo , A Argiolas , G Miscio , S Thomas , G P Piras , R Trevisan , P C Perin , S Bacci , L Zucaro , M Margaglione , L Frittitta , A Pizzuti , V Tassi , G C Viberti and V Trischitta Division and Research Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. endocrinologia@operapadrepio.it 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.