#2213 APOL1 high-risk genotype in in a Dutch multi-ethnic population
Authors: Manson Nienke , van Schijndel Emma , Ferwerda Bart , Galenkamp Henrike , Huisan Brechje , Vogt Liffert , Zwinderman Koos , Bemelman Frederike 
Published: May 2024

Abstract

Background and Aims
The presence of 2 APOL1 high-risk alleles (high-risk APOL1 genotype) is associated with an increased risk of ESKD. In the USA, the prevalence of these high-risk alleles is high in people of West African descent and almost absent in patients from European descent. In Amsterdam, there is a significant number of people from Surinam, and (West-) Africa. A big group of Surinamese individuals have a West African heritage. The prevalence, however, of high-risk APOL1 genotype in the Netherlands and thereby the significance is unknown. The aim of this research was to investigate the prevalence of the APOL1 risk alleles in a multi-ethnic cohort of the Amsterdam general population consisting of individuals of African Surinamese, Ghanaian, Moroccan and Dutch origin. Second we correlate the presence of these risk alleles to blood pressure, kidney function and proteinuria.

Method
HELIUS is a multi-ethnic prospective cohort study including people aged 18-70 who were randomly selected, stratified by ethnic origin, from the Amsterdam general population. Baseline examination took place tween 2011 and 2015. We analysed a population of 5971 individuals with available genotype data, of whom 1287 were of Dutch, 3048 of Moroccan, 1156 of African Suriname and 480 of Ghanaian descent. APOL1 risk was determined by genotyping two APOL1 missense variants, rs73885319A&gt;G, S342G; rs60910145T&gt;G, I384M, together constitute the G1 high-risk allele and the 6-base pair deletion allele, rs71785313 RRRATAA/−, N388Y399/−−, is the G2 high risk allele.
Logistic regression analyses were performed to determine correlation between creatinine, eGFR, and systolic blood pressure and apol1 high risk genotype, with additional adjustments for age, sex, and BMI.

Results
The prevalence of high-risk APOL1 genotype was 4.17% in the total sample, in African Surinamese 9.5%, and in the Ghanaian 29.0%. There were no individuals with high risk genotype in the Moroccan or Dutch descent population.
The presence of high risk APOL1 genotype was associated with an elevated creatinine level of 10.68 µmol/L (SD 0.91) in the whole cohort. Also, in the Surinamese and Ghanaian populations population the presence of the high-risk APOL1 genotype was associated with an increased creatinine of 2.6 µmol/L (SD 1.00) as compared to the black population with low-risk APOL1 genotype.
People with high-risk APOL1 genotype had significantly higher systolic blood pressure 10.69 mmHg (SD 0.091) than those without. Nevertheless, there was no significant difference in systolic blood pressure in the black population with high-risk APOL1 genotype in comparison with the black population with low-risk APOL1 genotype 1.38 mmHg (SD 1.17).
Also, there was no significant difference in eGFR (CKD CKD-EPI 2009) in any analysis and no differences in proteinuria was seen, between those with and without the high-risk APOL1 genotype.

Conclusion
In this population, the overall prevalence of the APOL1 risk alleles seems to conform to the African American population in the USA. There is however a much higher prevalence of high-risk APOL1 genotype in the Ghanaian in comparison to the African Surinamese. The group with high-risk APOL1 genotype had significantly higher creatinine levels and higher systolic blood pressure. However there was no significant difference in blood pressure within the black population between APOL1 high-risk genotype and low-risk genotype. There was no significant difference in eGFR, possibly because the CKD-EPI 2009 formula was used which overestimates the eGFR in the black population. Better calculation with cysteine C possibly gives different outcomes.
In conclusion, this is the first study in Europe investigating the prevalence of APOL1 high-risk genotype in a large population-based cohort. APOL1 risk alleles, and high-risk genotype, are prevalent in our population of African descent.
More analysis in this cohort are pending and also longitudinal data will follow.