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The prevalence of unique SNP s in the renin‐angiotensin system highlights the need for pharmacogenetics in Indigenous Australians
Author(s) -
Grimson Steven,
Cox Amanda J.,
Pringle Kirsty G.,
Burns Christine,
Lumbers Eugenie R.,
Blackwell C. Caroline,
Scott Rodney J.
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12525
Subject(s) - indigenous , snp , allele , single nucleotide polymorphism , genotype , genetics , allele frequency , renin–angiotensin system , angiotensin converting enzyme , biology , disease , medicine , gene , blood pressure , ecology
Summary Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms ( SNP s) 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, AGTR 1 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 SNP s 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 AGTR 1 (rs5186). Thus the prevalence of RAS SNP s in this Indigenous Australian desert community was different from non‐Indigenous Australians as was the prevalence of cytokine SNP s (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.