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Genetic Variants Associated With End-Stage Renal Disease

Last Updated: August 24, 2010.

Genetic variants in protein kinase C-β 1 genes, the genes implicated in the development of complications in diabetes, are associated with the risk of end-stage renal disease in Chinese individuals with type 2 diabetes, according to a study in the Aug. 25 issue of the Journal of the American Medical Association.

TUESDAY, Aug. 24 (HealthDay News) -- Genetic variants in protein kinase C-β 1 (PRKCB1) genes, the genes implicated in the development of complications in diabetes, are associated with the risk of end-stage renal disease (ESRD) in Chinese individuals with type 2 diabetes, according to a study in the Aug. 25 issue of the Journal of the American Medical Association.

To search for an association between ESRD and PRKCB1 polymorphisms, Ronald C.W. Ma, of the Prince of Wales Hospital in Hong Kong, and colleagues genotyped 18 single nucleotide polymorphisms (SNPs) spanning the PRKCB1 gene in a large cohort of Chinese subjects with type 2 diabetes -- but without renal disease -- recruited between 1995 and 1998. They validated their results in a second large prospective cohort of patients with early-onset diabetes, and used a cross-sectional cohort from an inpatient database to investigate the association between PRKCB1 genotype and quantitative measures of renal function.

The researchers found four common SNPs significantly associated with ESRD, which developed in 7.7 percent of the study patients after a mean of 7.9 years. The strongest association was found with the T allele at rs3760106 and the G allele at rs2575390; those alleles also displayed an association with development of chronic kidney disease in the validation cohort. In the joint effect analysis, the hazard ratio for ESRD increased with increasing number of risk alleles (P < .001); the adjusted risk for ESRD was 6.04 for patients who had four risk alleles compared to those who had zero or one risk allele.

"In summary, using two large prospective cohorts and a cross-sectional cohort of Chinese patients with type 2 diabetes, we found that genetic variants of the PRKCB1 gene were associated with incident ESRD, independent of confounders such as albuminuria, glycemia, retinopathy, and other risk factor control," the authors write.

Two authors disclosed financial relationships with pharmaceutical companies.

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