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The p53Pro72Arg Polymorphism is Associated with Albuminuria among Aboriginal Australians

Stephen P. McDonald^*, Wendy E. Hoy^*, Graeme P. Maguire^*, Natalia L. Duarte, David E. L. Wilcken and Xing L. Wang^¶

*Menzies School of Health Research, Darwin, Australia; Cardiovascular Genetics Department, Prince of Wales Hospital, Sydney, Australia; NT Clinical School, Flinders University of SA, Darwin, Australia; Faculty of Medicine, University of Sydney, Sydney, Australia; ^¶Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas.

Correspondence to: Dr. Stephen P. McDonald, ANZDATA Registry, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville SA 5011, Australia. Phone: 61-8-8222-6809; Fax: 61-8-8222-6402; E-mail: stephenm{at}anzdata.org.au

ABSTRACT. Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673