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

Duffy, David L., McDonald, Stephen P., Hayhurst, Beverley, Panagiotopoulos, Sianna, Smith, Trudy J., Wang, Xing L., Wilcken, David E., Duarte, Natalia L., Mathews, John and Hoy, Wendy E. (2016) Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53. BMC Nephrology, 17 183: 1-10. doi:10.1186/s12882-016-0396-2


Author Duffy, David L.
McDonald, Stephen P.
Hayhurst, Beverley
Panagiotopoulos, Sianna
Smith, Trudy J.
Wang, Xing L.
Wilcken, David E.
Duarte, Natalia L.
Mathews, John
Hoy, Wendy E.
Title Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53
Journal name BMC Nephrology   Check publisher's open access policy
ISSN 1471-2369
Publication date 2016-11-21
Year available 2016
Sub-type Article (original research)
DOI 10.1186/s12882-016-0396-2
Open Access Status Not yet assessed
Volume 17
Issue 183
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2017
Language eng
Formatted 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.
Keyword Albuminuria
Epidemiology
Genetics
Heritability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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Created: Thu, 24 Nov 2016, 22:21:37 EST by Wendy E Hoy on behalf of UQ Centre for Clinical Research