Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53

BMC Nephrology

Research Article

Natalia L. Duarte¹  David E. Wilcken¹  Wendy E. Hoy²  Beverley Hayhurst³  Xing L. Wang⁴  Sianna Panagiotopoulos⁵  David L. Duffy⁶  John Mathews⁷  Trudy J. Smith⁸  Stephen P. McDonald⁹ 

[1] Cardiovascular Genetics Department, Prince of Wales Hospital, Sydney, Australia;Centre for Chronic Disease, The University of Queensland School of Medicine, Brisbane, Australia;Centre for Chronic Disease, Central Clinical School, Royal Brisbane Hospital, 4029, Queensland, Australia;Cradle Coast Authority, Tasmania, Formerly Menzies School of Health Research, Darwin, Australia;Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, Australia;Department of Medicine, University of Melbourne, Melbourne, Australia;Genetic Epidemiology Laboratory, QIMR Berghofer Institute of Medical Research, 300 Herston Rd, 4006, Brisbane, Australia;Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia;Menzies School of Health Research, Darwin, Australia;The Queen Elizabeth Hospital, Adelaide, Australia;

关键词: Albuminuria;    Epidemiology;    Genetics;    Heritability;   

DOI  :  10.1186/s12882-016-0396-2

 received in 2015-11-01, accepted in 2016-11-09,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2016