Additive Effect of APOL1 Risk Variants on Creatinine in a Multiethnic Amsterdam Cohort

Background: The apolipoprotein L1 gene (APOL1) has two variants that are associated with an increased risk of kidney disease. These risk variants are only found in people of West African descent. Initially, two risk variants and a second-hit were thought to be necessary for increased risk of kidney disease, but recent studies from Africa and the USA suggest an additive effect. This study aimed to assess whether an additive hereditary pattern is present in our large multi-ethnic cohort. Methods: A cross-sectional analysis was performed with Dutch, African-Surinamese, Moroccan or Ghanaian participants from the Healthy Life in an Urban Setting (HELIUS) cohort. The APOL1 variants were determined by PCR or a TaqMan Assay. Primary outcome was the prevalence of APOL1 risk variants. Secondary outcome was the association between APOL1 risk variants and creatinine, evaluated by ethnicity-stratified multiple linear regression adjusted for age, sex, BMI, hypertension, and diabetes. Box-Cox transformation corrected for non-normality. Results: A total of 12 624 participants were included. 0.6% of Dutch and 2% of Moroccan participants carried one or more APOL1 risk variants. Of the African-Surinamese participants, 9.4% had two risk variants and 39.5% had one. In the Ghanaian group, 30.4% had two and 45.6% had one. Linear regression for creatinine showed a positive association with not only two but also one APOL1 risk variant in the African-Surinamese (1vs0 risk alleles: p<0.01; 2vs0: p<0.01; 2vs1: p=0.01). This difference was also apparent in the Ghanaians (1vs0: p= 0.03; 2vs0: p<0.01; 2vs1: p= 0.2; Figure 1). Conclusion: In conclusion, APOL1 risk variants are highly prevalent in the African-Surinamese and Ghanaian population in Amsterdam. We found evidence for an additive effect of APOL1 risk variants on creatinine levels, supporting the recent paradigm shift. Future efforts will focus on confirming the results longitudinally.Association between creatinine and APOL1 risk alleles.