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Sequencing rare and common APOL1 coding variants to determine kidney disease risk.
Kidney Int 2015; 88(4):754-63KI

Abstract

A third of African Americans with sporadic focal segmental glomerulosclerosis (FSGS) or HIV-associated nephropathy (HIVAN) do not carry APOL1 renal risk genotypes. This raises the possibility that other APOL1 variants may contribute to kidney disease. To address this question, we sequenced all APOL1 exons in 1437 Americans of African and European descent, including 464 patients with biopsy-proven FSGS/HIVAN. Testing for association with 33 common and rare variants with FSGS/HIVAN revealed no association independent of strong recessive G1 and G2 effects. Seeking additional variants that might have been under selection by pathogens and could represent candidates for kidney disease risk, we also sequenced an additional 1112 individuals representing 53 global populations. Except for G1 and G2, none of the 7 common codon-altering variants showed evidence of selection or could restore lysis against trypanosomes causing human African trypanosomiasis. Thus, only APOL1 G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN in the US population. Hence, in most potential clinical or screening applications, our study suggests that sequencing APOL1 exons is unlikely to bring additional information compared to genotyping only APOL1 G1 and G2 risk alleles.

Authors+Show Affiliations

Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.Center for Cancer Research Informatics Core, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), Gosselies, Belgium.Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.Laboratory of Experimental Immunology, Cancer and Inflammation Program, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI, Frederick National Laboratory, Frederick, Maryland, USA.Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.Caribbean Genome Center, Department of Biology, University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico.Caribbean Genome Center, Department of Biology, University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico.Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), Gosselies, Belgium.Kidney Disease Section, NIDDK, NIH, Bethesda, Maryland, USA.Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, NCI, Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland, USA.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25993319

Citation

Limou, Sophie, et al. "Sequencing Rare and Common APOL1 Coding Variants to Determine Kidney Disease Risk." Kidney International, vol. 88, no. 4, 2015, pp. 754-63.
Limou S, Nelson GW, Lecordier L, et al. Sequencing rare and common APOL1 coding variants to determine kidney disease risk. Kidney Int. 2015;88(4):754-63.
Limou, S., Nelson, G. W., Lecordier, L., An, P., O'hUigin, C. S., David, V. A., ... Winkler, C. A. (2015). Sequencing rare and common APOL1 coding variants to determine kidney disease risk. Kidney International, 88(4), pp. 754-63. doi:10.1038/ki.2015.151.
Limou S, et al. Sequencing Rare and Common APOL1 Coding Variants to Determine Kidney Disease Risk. Kidney Int. 2015;88(4):754-63. PubMed PMID: 25993319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequencing rare and common APOL1 coding variants to determine kidney disease risk. AU - Limou,Sophie, AU - Nelson,George W, AU - Lecordier,Laurence, AU - An,Ping, AU - O'hUigin,Colm S, AU - David,Victor A, AU - Binns-Roemer,Elizabeth A, AU - Guiblet,Wilfried M, AU - Oleksyk,Taras K, AU - Pays,Etienne, AU - Kopp,Jeffrey B, AU - Winkler,Cheryl A, Y1 - 2015/05/20/ PY - 2014/11/05/received PY - 2015/03/26/revised PY - 2015/04/02/accepted PY - 2015/5/21/entrez PY - 2015/5/21/pubmed PY - 2016/7/14/medline SP - 754 EP - 63 JF - Kidney international JO - Kidney Int. VL - 88 IS - 4 N2 - A third of African Americans with sporadic focal segmental glomerulosclerosis (FSGS) or HIV-associated nephropathy (HIVAN) do not carry APOL1 renal risk genotypes. This raises the possibility that other APOL1 variants may contribute to kidney disease. To address this question, we sequenced all APOL1 exons in 1437 Americans of African and European descent, including 464 patients with biopsy-proven FSGS/HIVAN. Testing for association with 33 common and rare variants with FSGS/HIVAN revealed no association independent of strong recessive G1 and G2 effects. Seeking additional variants that might have been under selection by pathogens and could represent candidates for kidney disease risk, we also sequenced an additional 1112 individuals representing 53 global populations. Except for G1 and G2, none of the 7 common codon-altering variants showed evidence of selection or could restore lysis against trypanosomes causing human African trypanosomiasis. Thus, only APOL1 G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN in the US population. Hence, in most potential clinical or screening applications, our study suggests that sequencing APOL1 exons is unlikely to bring additional information compared to genotyping only APOL1 G1 and G2 risk alleles. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/25993319/Sequencing_rare_and_common_APOL1_coding_variants_to_determine_kidney_disease_risk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2157-1716(15)32241-3 DB - PRIME DP - Unbound Medicine ER -