The prevalence of unique SNPs in the renin‐angiotensin system highlights the need for pharmacogenetics in Indigenous Australians

Abstract

Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms (SNPs) in genes of the renin-angiotensin system (RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations (P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines.

Programming of Renal Development and Chronic Disease in Adult Life

“…While there are genetic polymorphisms that contribute to this epidemic of CKD ( Duffy et al, 2016 ), some of those SNPs commonly associated with hypertension and CKD in other populations have a very low prevalence in Indigenous Central Australians ( Grimson et al, 2016 ). Conversely, the prevalence of the DD genotype in the ACE gene is higher in Indigenous Australians requiring dialysis than it is in healthy controls, suggesting that overactivity of the RAS exacerbates chronic renal disease ( Lester et al, 1999 ).…”

Evaluation of existing experimental evidence for treatment of depression in indigenous populations: A systematic review

“…In the field of Indigenous health research, one of the challenges is to overcome the mistrust among Indigenous communities who have been concerned about past misuse of specimens in genetic studies (Boyer et al, 2011). The differences in pharmacokinetics and pharmacodynamics between Indigenous and non-Indigenous populations have been noted in the context of various medical conditions and related medications (Grimson et al, 2016;Po, 2000;Yasuda, Zhang, & Huang, 2008). However, due to the methodological limitations of the trial assessing the tricyclic antidepressant treatment, it is not possible to propose conclusive recommendations.…”