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BMC Nephrology
Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53

Authors: David L. Duffy, Stephen P. McDonald, Beverley Hayhurst, Sianna Panagiotopoulos, Trudy J. Smith, Xing L. Wang, David E. Wilcken, Natalia L. Duarte, John Mathews, Wendy E. Hoy

Published in: BMC Nephrology | Issue 1/2016

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Abstract

Background

Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.

Methods

Using results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR).

Results

In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h2 = 64%) and blood pressure (sBP h2 = 29%, dBP, h2 = 11%) were significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72 polymorphisms (P = 0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident.

Conclusions

While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.
Appendix
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Metadata
Title
Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53
Authors
David L. Duffy
Stephen P. McDonald
Beverley Hayhurst
Sianna Panagiotopoulos
Trudy J. Smith
Xing L. Wang
David E. Wilcken
Natalia L. Duarte
John Mathews
Wendy E. Hoy
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0396-2

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