Ace and TP53 Gene Variants Modulate Risk of Albuminuria in Aboriginal Australians

Ace and TP53 Gene Variants Modulate Risk of Albuminuria in Aboriginal Australians Journal Article

Nephrology

  • Author(s): Hoy, W, Duffy, D, McDonald, S
  • Published: 2016
  • Volume: 21(Suppl 2)

Abstract: Background: Australian Aboriginal people have high rates of albuminuria, CKD, hypertension, cardiovascular disease and diabetes. There is little information about possible genetic contributors. Aim: To test for familial aggregation of diabetes, blood pressure, albuminuria (UACR) and eGFR, and quantify the contribution of four candidate genes (ACE; TP53; ENOS3; MTHFR). Methods: In one high risk remote Northern Territory (NT) community, we determined familial relationships of 357 individuals selected to represent the community's UACR profile, and genotyped for six polymorphisms at the four loci. We also recorded UACR, BP, eGFR and diabetes status. Results: Log‐transformed UACR was the most heritable trait (heritability h2 64%), but BP also had a significant familial contribution (sBP h2 = 24%, dBP = 11%). 10% of the genetic variance of UACR was explained by the ACE insertion‐deletion polymorphism (P = 0.0003), and 5% by the TP53 codon72 polymorphism (P = 0.007). Each ACE D allele increased UACR 2.7 fold, and TP53*P72 allele, 1.6‐fold. ACE D/I carriers had higher SBP (130.4 versus 119.2 mm Hg) and DBP (83.3 versus 70.7 mm Hg), than I/I carriers, and were four times more often diabetic (22% versus 5%). Conclusions: As in other populations, risks of albuminuria and hypertension are partially determined by genetic factors. The relationship of the ACE D allele with CKD is similar to other populations, especially in diabetic nephropathy. Associations of the p53 variant have been reported in only one other setting, also a remote NT Aboriginal community, with similar findings. We note that the p53 codon72 arginine variant protein induces apoptosis more effectively than the proline variant, and may predispose to diabetes. Moreover, p53 inhibition enhances renal fibrosis in some models, and exacerbates other renal pathologies eg experimental Alport Syndrome.

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Suggested Citation
Hoy, W, Duffy, D, McDonald, S, 2016, Ace and TP53 Gene Variants Modulate Risk of Albuminuria in Aboriginal Australians, Volume:21(Suppl 2), Journal Article, viewed 09 August 2022, https://www.nintione.com.au/?p=14289.

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