Polymorphisms of the Protein Kinase C-β Gene (PRKCB1) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria
- Shin-ichi Araki, MD, PHD1,
- Masakazu Haneda, MD, PHD2,
- Toshiro Sugimoto, MD, PHD1,
- Motohide Isono, MD, PHD1,
- Keiji Isshiki, MD, PHD1,
- Atsunori Kashiwagi, MD, PHD1 and
- Daisuke Koya, MD, PHD13
- 1Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
- 2Second Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan
- 3Division of Endocrinology and Metabolism, Department of Medicine, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan
- Address correspondence and reprint requests to Shin-ichi Araki, MD, PhD, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. E-mail: araki{at}belle.shiga-med.ac.jp
Abstract
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 1.0–5.2]), 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.
- AER, albumin excretion rate
- eGFR, estimated glomerular filtration rate
- MDRD, Modification of Diet in Renal Disease
- PKC, protein kinase C
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 January 2, 2005.
- Received September 14, 2005.
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