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, MD1,
- Roberto Trevisan, MD2,
- Michele Dalla Vestra, MD3,
- Monica Vedovato, MD2,
- Alessandra Argiolas, PHD4,
- Anna Solini, MD5,
- Alois Saller, MD3,
- Francesco Damone, MD1,
- Antonio Tiengo, MD2,
- Vincenzo Trischitta, MD16 and
- Paola Fioretto, MD3
- 1Unit of Endocrinology, Scientific Institute “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
- 2Department of Clinical Medicine, University of Padova, Padova, Italy
- 3Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
- 4Scientific Institute CSS-Mendel, Rome, Italy
- 5Department of Internal Medicine, University of Pisa, Pisa, Italy
- 6Department of Clinical Science, University “La Sapienza,” Rome, Italy
- Address correspondence and reprint requests to Vincenzo Trischitta, MD, Unit of Endocrinology, Scientific Institute “Casa Sollievo della Sofferenza,” 71013 San Giovanni Rotondo (FG), Italy. E-mail: vincenzo.trischitta{at}uniroma1.it
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 AvaII 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/m2), 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.
- AER, albumin excretion rate
- DN, diabetic nephropathy
- GFR, glomerular filtration rate
- Vv(mes/glom), fractional volume of the glomerulus occupied by mesangium
- Vv(MM/glom), fractional volume of the glomerulus occupied by mesangial matrix
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted July 12, 2003.
- Received June 2, 2003.
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