BACKGROUND: Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D. PREDICTOR: The ENPP1 Q121 variant. MEASUREMENTS: Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A(1c), triglycerides, total cholesterol, and high-density lipoprotein cholesterol. OUTCOMES: Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m(2)). RESULTS: In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04). LIMITATIONS: P values not approaching a genome-wide level of significance. CONCLUSIONS: Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
BACKGROUND:Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D. PREDICTOR: The ENPP1 Q121 variant. MEASUREMENTS: Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A(1c), triglycerides, total cholesterol, and high-density lipoprotein cholesterol. OUTCOMES: Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m(2)). RESULTS: In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04). LIMITATIONS: P values not approaching a genome-wide level of significance. CONCLUSIONS: Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
Authors: A Pizzuti; L Frittitta; A Argiolas; R Baratta; I D Goldfine; M Bozzali; T Ercolino; G Scarlato; L Iacoviello; R Vigneri; V Tassi; V Trischitta Journal: Diabetes Date: 1999-09 Impact factor: 9.461
Authors: Salvatore De Cosmo; Antonio Minenna; Oznelle Ludovico; Sandra Mastroianno; Anna Di Giorgio; Leonardo Pirro; Vincenzo Trischitta Journal: Diabetes Care Date: 2005-04 Impact factor: 19.112
Authors: P Fioretto; M Mauer; E Brocco; M Velussi; F Frigato; B Muollo; M Sambataro; C Abaterusso; B Baggio; G Crepaldi; R Nosadini Journal: Diabetologia Date: 1996-12 Impact factor: 10.122
Authors: Kasper Rossing; Per K Christensen; Peter Hovind; Lise Tarnow; Peter Rossing; Hans-Henrik Parving Journal: Kidney Int Date: 2004-10 Impact factor: 10.612
Authors: David Meyre; Nabila Bouatia-Naji; Agnès Tounian; Chantal Samson; Cécile Lecoeur; Vincent Vatin; Maya Ghoussaini; Christophe Wachter; Serge Hercberg; Guillaume Charpentier; Wolfgang Patsch; François Pattou; Marie-Aline Charles; Patrick Tounian; Karine Clément; Béatrice Jouret; Jacques Weill; Betty A Maddux; Ira D Goldfine; Andrew Walley; Philippe Boutin; Christian Dina; Philippe Froguel Journal: Nat Genet Date: 2005-07-17 Impact factor: 38.330
Authors: Salvatore De Cosmo; Sabrina Prudente; Olga Lamacchia; Daniela Lucchesi; Hetal Shah; Christine Mendonca; Laura Pucci; Luana Mercuri; Ernest V Gervino; Thomas H Hauser; Diego Bailetti; Giuseppe Penno; Mauro Cignarelli; Alessandro Doria; Vincenzo Trischitta Journal: Nephrol Dial Transplant Date: 2012-05-23 Impact factor: 5.992