Polymorphisms of the Protein Kinase C-β Gene (PRKCB1) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria

Araki, Shin-Ichi; Haneda, Masakazu; Sugimoto, Toshiro; Isono, Motohide; Isshiki, Keiji; Kashiwagi, Atsunori; Koya, Daisuke
April 2006
Diabetes Care;Apr2006, Vol. 29 Issue 4, p864
Academic Journal
OBJECTIVE -- We investigated the contribution of PKC-β gene (PRKCB1) polymorphisms to diabetic kidney disease in a prospective observational follow-up study. RESEARCH DESIGN AND METHODS -- A total of 364 Japanese subjects with type 2 diabetes without overt proteinuria were enrolled during 1996-1998 and followed until 2004. Five single nucleotide polymorphisms (-1504C/T, -546C/G, -348A/G, -278C/T, and -238C/G) in the promoter region of PRKCB1 were genotyped. The end points were transition from stage to stage of diabetic nephropathy as a time-to-event outcome and the annual decline rate of estimated glomerular filtration rate (eGFR) as a slope-based outcome. RESULTS -- During the study (median 6 years), 34 of 364 subjects (9.3%) progressed. Kaplan-Meier estimation revealed that subjects with both T allele at - 1054 C/T and G allele at -546 C/G polymorphisms frequently showed transition to advanced stages of diabetic nephropathy (P = 0.015). The annual change rate in eGFR in the subjects with both alleles was also significantly higher than in others (-2.96 ± 0.62 vs. -1.63 ± 0.15 ml/min per 1.73 m2/year, P = 0.02). The estimated frequency of this risk T-G haplotype was significantly higher in the progressors who showed transition to advanced nephropathy stages (12%) than in the nonprogressors (5%) (odds ratio. 2.3 [95% CI 1.0-5.21), and it was also higher in those with accelerated decline of the Δ eGFR (≥3 ml/min per 1.73 m2/year) than in those without (2.1 [1.1-3.9]). CONCLUSIONS -- Our study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes.


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