Insertion in APOL1‐Like Gene is Associated with Increased Blood Pressure but Not Renal Dysfunction in African Green Monkeys
Authors: Barrett Lucas D G , Weaver Chelsea C , Rhoads Megan K , Taylor Jessica C , Osborn Jeffrey L 
Published: June 2021

Hypertension (HTN) is a known major risk factor for many causes of human mortality, such as kidney disease, stroke, and heart failure. Apolipoprotein L‐I (APOL1) is a component of HDL with an innate ability to lyse the Trypanosoma brucei, a parasite native to Africa known to cause African sleeping sickness. The biological vector and most common path of transmission for the parasite is the tsetse fly. In humans, two variant alleles of APOL1 have been identified that protect against some of the subspecies of T. brucei that cause African sleeping sickness. Both of these variants are associated with increased risk of developing end stage renal disease (ESRD), particularly in individuals of west African descent. In order to better understand the APOL1‐mediated pathogenesis of ESRD, a translational model that closely recapitulates the human phenotype is needed. The current study utilizes the African Green Monkey (AGM; Chlorocebus aethiops sabaeus), a novel model of spontaneous HTN with renal glomerular pathologies and origins in west Africa. Previously, we reported the presence of an 18‐nucleotide insertion in the APOL1‐like gene in AGMs. We hypothesized that AGMs with the APOL1‐like insertion will have increased blood pressure and reduced renal function compared to animals without the insertion. Systolic (SBP) and diastolic (DBP) blood pressures and heart rates were measured with a Doppler stethoscope and forearm plethysmography followed by systemic venous blood collection. Daily urine output and water intake was collected from single‐housed AGMs daily for three consecutive days. Urinary protein and creatinine were measured using standard colorimetric techniques. Urine sodium concentration was measured by flame photometry. SBP was higher for homozygotes with the insertion (HOM; 205.8 ± 20.5 mmHg, n = 4) compared to both heterozygotes (HET; 135.6 ± 8.4 mmHg, n = 24) and animals without the insertion (NI; 141.1 ± 6.0 mmHg, n = 46; p < 0.05). DBP was higher for HOM AGMs (108.8 ± 13.0 mmHg) compared to both HET and NI animals (HET 64.1 ± 5.4 mmHg; NI 69.8 ± 3.8 mmHg; p < 0.05). Heart rate, water intake, urine flow rate, estimated glomerular filtration rate, Na+ excretion, and protein excretion were not different among all groups (p > 0.05). Thus, HOM insertion in the APOL1‐like gene in the AGM is associated with increased SBP and DBP. Presently, there is no evidence of an association between the insertion in the APOL1‐like gene and renal dysfunction. This may be due to short‐term rather than longitudinal data collection, as renal dysfunction is dependent on age in HOM human carriers of the APOL1 variants. Future studies will focus on changes in renal function over time in HOM, HET, and NI AGMs. Additionally, breeding groups have been established with HOM male and HET female AGMs to expand the incidence of HOM allele expression and determine the effect of environmental factors on the development of HTN and ESRD in HOM, HET, and NI AGMs. This model organism will allow examination of possible links between HTN and APOL1‐like genetic variants that may lead to new targets and therapies for treatment of patients with APOL1‐related renal dysfunction and ESRD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.