PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients.
BACKGROUND
Recently, an amino acid variant (K121Q) in the glycoprotein PC-1 (Q allele) has been associated with faster progression of diabetic nephropathy, as estimated by calculated creatinine clearance. We tested the impact of the PC-1 (K121Q) variant on loss of glomerular filtration rate (GFR) measured by the [(51)Cr]EDTA plasma clearance technique.


METHODS
We performed an observational follow-up study of 295 (182 males) type 1 patients with diabetic nephropathy [mean age 37 (SE 0.7) years, mean duration of diabetes 23 (SE 0.5) years]. All patients were followed for at least 3 years, median 8 years (range 3-17), with at least three measurements of GFR using [(51)Cr]EDTA (median 11 measurements (range 3-32)). Two hundred and seventeen patients had the KK genotype and 78 carried the Q allele (71 KQ and 7 QQ).


RESULTS
Patients carrying the Q allele had a mean rate of decline in GFR during follow-up of 3.6 ml/min per year (SE 0.4) compared with 4.0 ml/min per year (SE 0.3) in patients with the KK genotype. Other risk factors for progression of diabetic nephropathy were similar in Q carriers and KK carriers. When dividing patients in tertiles based on rate of decline in GFR, we found no difference in distribution of K121Q genotypes. No difference in the number of patients who died or reached end-stage renal disease during follow-up according to K121Q genotype were found. A multiple linear regression analysis revealed that albuminuria, mean arterial blood pressure, haemoglobin A(1C) and serum cholesterol during follow-up predicted a steeper decline in GFR [R(2) (adjusted)=0.27], whereas the PC-1 genotype did not contribute.


CONCLUSIONS
Our study did not reveal an association between the PC-1 amino acid variant K121Q and progression of diabetic nephropathy.
Jacobsen
Peter
P
Steno Diabetes Center, Gentofte, Denmark. pkjocobsen@dadlnet.dk
Grarup
Niels
N
Tarnow
Lise
L
Parving
Hans-Henrik
HH
Pedersen
Oluf
O
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D013997:Time Factors
D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases