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

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.