APOL 1 Risk Genotype is associated with Albuminuria in Sub-Saharan African without Hypertension: A Case Study of Trypanosoma Brucei Gambiense Endemic Area

Purpose. An association between APOL1 risk genotypes (HRG) and hypertension has been reported in African Americans with chronic kidney diseases (CKD). However, such data from African populations living in a Human African Trypanosomiasis (HAT) endemic area remain limited.This study assessed the association between APOL1 high-risk genotypes (HRG) and hypertension among sub-Saharan African in T.b. gambiense endemic area. Methodology. This cross-sectional study enrolled 94 HAT-infected and 144 non–infected participants in Masimanimba, the Democratic Republic of the Congo, from April 2019 to April 2021. We evaluated the association between APOL1 HRG and hypertension in HAT-infected and non–infected participants. APOL1 HRG was defined as the presence of two risk variants (G1/G1, G2/G2, or G1/G2), and a low-risk genotype (LRG) with the presence of 0 or 1 single variant. The elevated albuminuria was defined as urinary albumin/creatinine ratio ≥ 30 mg/g. Student’s and Pearson's Chi2 tests or Fisher’s exact test were used to compare means and proportions. The Wilcoxon/Mann–Whitney test was used to compare medians. A multivariate logistic regression model was used to identify independent determinants of hypertension. Odds ratios were provided with their 95% confidence intervals (Cis). Statistical significance was set at p < 0.05, based on 2-tailed test. Findings. APOL1 sequence analysis revealed that 3 of 21 (14.3%) hypertensive participants carried HRG (G1G1) and 7 of 103 (6.8%) non-hypertensive carried HRG (G1G1, G2G2, and G1G2) (p=0.371). The frequency of APOL1 HRG among hypertensive participants was 14.3% in both HAT- infected and uninfected individuals. Ten of 21 (47.6%) hypertensive individuals with elevated albuminuria had a higher incidence of CKD (100% vs.  0%; p < 0.001) and HRG (30% vs. 0%; p = 0.09) than 11 (52.3%) without albuminuria who carried LRG. Of 103 non-hypertensive subjects, 43 (41.7%) with elevated albuminuria had a higher frequency of HRG (16.3% vs. 0%; p = 0.002) and CKD (100% vs. 1.7%; p<0.001) compared with 60 of 103 (58.3%) without albuminuria who carried LRG. Unique contributor to theory, policy and practice:  APOL1 HRG was associated with albuminuria and CKD, regardless of the hypertension status in T.b. gambiense HAT endemic area. However, further prospective cohort studies are required to confirm these results. The High-risk subjects will benefit from early preventive measures in low-income countries.