APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume

Kidney Int. 2016 Aug;90(2):440-449. doi: 10.1016/j.kint.2016.04.027. Epub 2016 Jun 22.

Abstract

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.

Keywords: APOL1; African Americans; brain; cognition; hypertension; magnetic resonance imaging; type 2 diabetes mellitus.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Americans / genetics
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Blood Pressure
  • Brain / blood supply
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Cerebral Small Vessel Diseases / epidemiology*
  • Cerebral Small Vessel Diseases / genetics
  • Cognition
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Glomerular Filtration Rate
  • Gray Matter / anatomy & histology*
  • Gray Matter / diagnostic imaging
  • Humans
  • Hypertension / epidemiology
  • Kidney Diseases / complications
  • Kidney Diseases / genetics*
  • Kidney Function Tests
  • Lipoproteins, HDL / genetics*
  • Magnetic Resonance Imaging
  • Randomized Controlled Trials as Topic
  • Risk
  • White Matter / anatomy & histology*
  • White Matter / diagnostic imaging

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL