PC-1 amino acid variant Q121 is associated with a lower glomerular filtration rate in type 2 diabetic patients with abnormal albumin excretion rates

Salvatore De Cosmo, Roberto Trevisan, Michele Dalla Vestra, Monica Vedovato, Alessandra Argiolas, Anna Solini, Alois Saller, Francesco Damone, Antonio Tiengo, Vincenzo Trischitta, Paola Fioretto

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE - To study the relationships between the PC-1 K121Q variant and diabetic nephropathy (DN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 125 patients with type 2 diabetes and abnormal albumin excretion rate (AER) (range 20-5,416 μg/min) were followed up for 4 years with repeated measurements of glomerular filtration rate (GFR). Genomic DNA was extracted from all patients, and the PC-1 K121Q polymorphism was determined by the PCR Avall restriction enzyme. A subset of 64 patients underwent a percutaneous kidney biopsy at baseline, and glomerular structure was analyzed by electron microscopic morphometric analysis. At baseline, age (56 ± 8 vs. 59 ± 7 years), BMI (28.3 ± 4.3 vs. 28.6 ± 3.7 kg/m 2), known duration of type 2 diabetes (11.1 ± 7 vs. 11.9 ± 8 years), and HbA1c (8.6 ± 1.8 vs. 8.4 ± 1.7%) were similar in K121K (KK, n = 87, 73 men/14 women) and XQ (35 K121Q + 3 Q121Q, n = 38, 27 men/11 women) patients. Baseline GFR was 96 ± 28 ml · min-1 · 1.73 m-2 and was related (P = 0.01-0.001) to age, known diabetes duration, and systolic blood pressure. RESULTS - XQ patients had lower GFR (P <0.05) than KK patients (88 ± 30 vs. 100 ± 26 ml · min-1 · 1.73 m-2); this difference persisted also after factoring in age and known diabetes duration. The rate of progression of DN was similar in KK and XQ patients: %ΔGFR was 4.1/year (median, range: 22.9-30.6) vs. 4.2/year (9.8-26.7). Morphometric parameters of diabetic glomerulopathy were similar in the two genotype groups. CONCLUSIONS - Among patients with type 2 diabetes with abnormal AER, those carrying the Q PC-1 genotype have more severe DN but not a faster GFR decline than KK patients, thus suggesting faster DN development since diabetes diagnosis in XQ patients.

Original languageEnglish
Pages (from-to)2898-2902
Number of pages5
JournalDiabetes Care
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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