Abstract
BackgroundAboriginal 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.MethodsUsing 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).ResultsIn 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.ConclusionsWhile 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0396-2) contains supplementary material, which is available to authorized users.
Highlights
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
Using data from another Aboriginal community we have previously shown that variants in two other much studied genes, the at four candidate genes (ACE) insertion-deletion and Tumour protein p53 gene (TP53)*R72P polymorphisms, are associated with albuminuria and hypertension [1]
We have reported a number of studies involving this Australian Aboriginal community [2, 4,5,6,7,8,9,10], documenting much higher rates of diabetes mellitus, arterial hypertension, albuminuria and renal disease than are seen in the general Australian population
Summary
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 likely Chronic diseases such as diabetes mellitus, hypertension, ischaemic heart disease, and chronic renal failure are far more common among Aboriginal Australians than they are in Australians of European descent [2,3,4,5]. Duffy et al BMC Nephrology (2016) 17:183 other ethnic groups: strikingly, the five-fold difference in incidence of renal diseases between African and European descended populations is largely due to two coding variants in the APOL1 gene [10,11,12,13] Using data from another Aboriginal community we have previously shown that variants in two other much studied genes, the ACE insertion-deletion (indel) and TP53*R72P polymorphisms, are associated with albuminuria and hypertension [1]. The latter is involved in regulating responses to DNA damage, whether repair or programmed cell death
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