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

American Journal of Nephrology
Gregory A HawkinsCarl D Langefeld

Abstract

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. 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. 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 <2 APOL1 G1 and/or G2 alleles (849 cases; 1,139 controls), the APOL3 null variant was nominally associated with ESK...Continue Reading

Citations

Oct 26, 2016·Scientific Reports·Douglas F DluzenMichele K Evans
Mar 25, 2017·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Karl L SkoreckiDavid J Friedman
Feb 2, 2018·Current Opinion in Nephrology and Hypertension·Jeffrey B KoppKoji Okamoto
Feb 24, 2018·Journal of the American Society of Nephrology : JASN·Florian Kronenberg
Dec 24, 2019·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·XiuHua WengXinHua Lin
Oct 4, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Erika R DruryKenneth J Mukamal
Dec 31, 2020·Physiological Reports·Chao ZhangFan Fan
Nov 22, 2016·Current Opinion in Lipidology·Florian Kronenberg

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