The p53Pro72Arg polymorphism is associated with albuminuria among aboriginal Australians.
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.
McDonald
Stephen P
SP
*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.
Hoy
Wendy E
WE
*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.
Maguire
Graeme P
GP
*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.
Duarte
Natalia L
NL
*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.
Wilcken
David E L
DEL
*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.
Wang
Xing L
XL
*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.
D000328:Adult; D000419:Albuminuria / Q000235:genetics* / Q000503:physiopathology; D000595:Amino Acid Sequence / Q000235:genetics; D001315:Australia; D005006:Ethnicity; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53