Re-Sequencing of the APOL1 - APOL4 and MYH9 Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression

Gregory A. Hawkins, David J. Friedman, Lingyi Lu, David R. McWilliams, Jeff W. Chou, Satria Sajuthi, Jasmin Divers, Rulan S. Parekh, Man Li, Giulio Genovese, Martin R. Pollack, Pamela J. Hicks, Donald W. Bowden, Lijun Ma, Barry I. Freedman, Carl D. Langefeld

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In African Americans (AAs), APOL1 G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the APOL1 loci, since earlier age ESKD is observed in some AAs with one APOL1 renal-risk variant, and because the adjacent gene MYH9 is associated with nephropathy in populations lacking G1 and G2 variants. Methods: Re-sequencing was performed across a ∼275 kb region encompassing the APOL1-APOL4 and MYH9 genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single APOL1 G1 or G2 risk variant. Results: Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare APOL3 Gln58Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for APOL1 G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalAmerican Journal of Nephrology
Volume42
Issue number2
DOIs
StatePublished - Oct 16 2015
Externally publishedYes

Keywords

  • African Americans
  • APOL1
  • DNA sequencing
  • FSGS
  • Genetics
  • Kidney disease

ASJC Scopus subject areas

  • Nephrology

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