Engulfment and cell motility 1 (ELMO1) and apolipoprotein A1 (APOA1) as candidate genes for sickle cell nephropathy

Br J Haematol. 2021 May;193(3):628-632. doi: 10.1111/bjh.17224. Epub 2020 Nov 20.

Abstract

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy.

Keywords: APOA1; APOL1; ELMO1; kidney disease; sickle cell disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing* / biosynthesis
  • Adaptor Proteins, Signal Transducing* / genetics
  • Adult
  • Albuminuria / genetics
  • Albuminuria / metabolism
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / metabolism
  • Animals
  • Apolipoprotein A-I* / biosynthesis
  • Apolipoprotein A-I* / genetics
  • Cell Movement / genetics*
  • Down-Regulation*
  • Female
  • Gene Regulatory Networks*
  • Humans
  • Male
  • Mice
  • Renal Insufficiency, Chronic* / genetics
  • Renal Insufficiency, Chronic* / metabolism
  • Up-Regulation*

Substances

  • APOA1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apolipoprotein A-I
  • ELMO1 protein, human