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Genetic variations associated with incident ESRD in Chinese patients with diabetes

Ma RCW. JAMA. 2010;304:881-889.

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New findings suggest that genetic variations in the protein kinase C-beta 1 gene were independently associated with incident end-stage renal disease in Chinese patients with type 2 diabetes.

Asian populations are at increased risk for kidney failure from diabetes and have a higher risk for ESRD when compared with whites, according to the researchers. For this study, researchers set out to assess the protein kinase C–beta 1 (PRKCB1) gene and the possible association with the development of new-onset ESRD in this population.

The study included 1,172 Chinese patients with type 2 diabetes diagnosed between 1995 and 1998 who did not have renal disease at baseline.

After an average of 7.9 years, 7.7% of patients had ESRD. Of the 18 common single nucleotide polymorphisms studied, four genetic variants predicted ESRD (P<.05). The likelihood for ESRD increased with a greater number of risk alleles (P<.001).

Compared with an incidence of 4.4 per 1,000 person-years in patients with one or no risk alleles (95% CI, 0.5-8.2), the incidence for ESRD was increased by 20 per 1,000 person-years in patients with four risk alleles (95% CI, 8.8-31.1). Moreover, the adjusted risk for ESRD in patients with four risk alleles vs. patients with no or one risk allele was 6.04 (95% CI, 2.0-18.31).

“In this study of Chinese patients with type 2 diabetes followed for 8 years, we found that genetic variants of the PRKCB1 gene were associated with development of incident ESRD independent of other known risk factors, with joint effects among the risk-conferring alleles,” the researchers wrote. “These associations persist despite correction for retinopathy, albuminuria, renal function, risk factor control, and use of medications including angiotensin-converting enzyme inhibitors at baseline.”

Researchers then studied an additional 1,049 patients with early onset type 2 diabetes who did not have renal disease at baseline and were recruited after 1998. Of these patients, 14.3% developed chronic kidney disease during follow-up. Further, a significant association was observed between CKD and the T-allele rs3760106 (HR=2.25; 95% CI, 1.31-3.87; P=.003) and the G-allele rs2575390 (HR=2.26; 95% CI, 1.31-3.88; P=.003).

“Our consistent results … suggest that genetic variation in the PRKCB1 gene is an important determinant for the risk of developing [diabetic kidney disease] in Chinese patients with type 2 diabetes,” the researchers concluded.

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