Absence of APOL1 risk alleles in a remote living Australian Aboriginal group with high rates of CKD, hypertension, diabetes, and cardiovascular disease
Authors: W.E. Hoy, J.B. Kopp, S.A. Mott, C.A. Winkler
Journal: Kidney International (2017)

Absence of apolipoprotein L1 (APOL1) gene risk allele variants G1 and G2 was reported in Indian patients with chronic kidney disease by Yadav et al. in their letter to the editor.1Yadav A.K. Kumar V. Sinha N. et al.APOL1 risk allele variants are absent in Indian patients with chronic kidney disease.Kidney Int. 2016; 90: 906-907Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Chronic kidney disease, hypertension, and type 2 diabetes are very common among Aboriginal people in remote areas of Australia. APOL1 risk alleles were absent in 234 Aboriginal Australians or 25% of adult participants in a health screen in one remote community, and in whom levels of albuminuria reflected those in the whole community. Albumin/creatinine ratio levels were at or above the traditional microalbuminuria threshold of 3.4 g/mol (30 mg/dl) in one-half of all adults, and in one-half of these the albumin/creatinine ratio levels were ≥ 34 g/mol.2Hoy W.E. Mathews J.D. McCredie D.A. et al.The multidimensional nature of renal disease: rates and associations of albuminuria in an Australian Aboriginal community.Kidney Int. 1998; 54: 1296-1304Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar The APOL1 status of those individuals, who were genotyped at the National Institutes of Health in the United States in 2009, was the reference ancestral genotype, G0/G0. Thus, the association of chronic kidney disease with APOL1 risk alleles was not identified in this group. Recent genetic evidence suggests that ancestors of modern Aboriginal Australians descended from a single migration out of Africa about 72,000 years ago.3Mallick S. Li H. Lipson M. et al.The Simons Genome Diversity Project: 300 genomes from 142 diverse populations.Nature. 2016; 538: 201-206Crossref PubMed Scopus (672) Google Scholar Aboriginal ancestors split from the main group of modern humans 58,000 years ago and arrived in Australia 50,000 years ago. It is estimated that APOL1 renal risk variants G1 and G2 arose in sub-Saharan Africans about 5000 to 10,000 years ago, well after the out-of-Africa migration of modern humans.4Friedman D.J. Pollak M.R. The genetics of kidney failure and the evolving story of APOL1.J Clin Invest. 2011; 121: 3367-3374Crossref PubMed Scopus (99) Google Scholar In view of their putative isolation in Australia after these major migrations, all Australian Aboriginals without recent African American admixture most likely lack G1 and G2 APOL1 risk alleles.3Mallick S. Li H. Lipson M. et al.The Simons Genome Diversity Project: 300 genomes from 142 diverse populations.Nature. 2016; 538: 201-206Crossref PubMed Scopus (672) Google Scholar, 4Friedman D.J. Pollak M.R. The genetics of kidney failure and the evolving story of APOL1.J Clin Invest. 2011; 121: 3367-3374Crossref PubMed Scopus (99) Google Scholar APOL1 risk allele variants are absent in Indian patients with chronic kidney diseaseKidney InternationalVol. 90Issue 4PreviewApolipoprotein L1 (APOL1) gene risk allele variants (G1 and G2) are strongly associated with focal segmental glomerulosclerosis, human immunodeficiency virus–associated nephropathy, and development, as well as progression of chronic kidney disease (CKD) in subjects with African ancestry.1 India is home to one-sixth of the world’s population and has witnessed a rapid rise in the burden of CKD, including CKD of unknown etiology. Out of many possible causes, the role of genetic predisposition has been suggested. Full-Text PDF Open Archive