title: Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Genetic Epidemiology Laboratory, QIMR Berghofer Institute of Medical Research, 300 Herston Rd, Brisbane, 4006, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.affiliation: The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: McDonald
authors.affiliation: Cradle Coast Authority, Tasmania, Formerly Menzies School of Health Research, Darwin, Australia.
authors.forename: Beverley
authors.initials: B
authors.lastname: Hayhurst
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Sianna
authors.initials: S
authors.lastname: Panagiotopoulos
authors.affiliation: Menzies School of Health Research, Darwin, Australia.
authors.forename: Trudy J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, Australia.
authors.forename: Xing L
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Cardiovascular Genetics Department, Prince of Wales Hospital, Sydney, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Wilcken
authors.affiliation: Cardiovascular Genetics Department, Prince of Wales Hospital, Sydney, Australia.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Duarte
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Mathews
authors.affiliation: Centre for Chronic Disease, The University of Queensland School of Medicine, Brisbane, Australia.|Centre for Chronic Disease, Central Clinical School, Royal Brisbane Hospital, Queensland, 4029, Australia.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Hoy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000235:genetics* / Q000652:urine; D062186:Arterial Pressure / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics; D003404:Creatinine / Q000652:urine; D005260:Female; D016158:Genes, p53; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D054643:INDEL Mutation; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010375:Pedigree; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A
keywords: Albuminuria; Epidemiology; Genetics; Heritability