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. 2016 Nov 21;17(1):183.
doi: 10.1186/s12882-016-0396-2.

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

David L Duffy  1 , Stephen P McDonald  2 , Beverley Hayhurst  3 , Sianna Panagiotopoulos  4 , Trudy J Smith  5 , Xing L Wang  6 , David E Wilcken  7 , Natalia L Duarte  7 , John Mathews  8 , Wendy E Hoy  9   10
Affiliations

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

David L Duffy et al. BMC Nephrol. .

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.

Keywords: Albuminuria; Epidemiology; Genetics; Heritability.

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Figures

Fig. 1
Fig. 1
Urinary albumin:creatinine ratio versus ACE insertion-deletion genotype in a sample of Aboriginal Australians. Lines at UACR of 3.4 and 30 g/mol represent suggested diagnostic thresholds for micro- and macroalbuminuria. The notches represent 95 % confidence intervals around the median of each group
Fig. 2
Fig. 2
Effect of ACE insertion-deletion genotype on cross-sectional relationship between age and UACR. Upper curve is D/I genotype group; lower, the I/I genotype group; the dotted line is the overall curve (Flattening of D/I curve after the age of 40 may reflect selective mortality, but there may be other cohort effects acting)
Fig. 3
Fig. 3
Effect of ACE insertion-deletion genotype on cross-sectional relationship between age and diastolic blood pressure. Upper curve is D/I genotype group; lower, the I/I genotype group; the dotted line is the overall curve
Fig. 4
Fig. 4
Effect of ACE insertion-deletion genotype on fasting plasma glucose
See this image and copyright information in PMC

References

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