APOL1 risk alleles among individuals with CKD in Northern Tanzania: A pilot study

Abstract

IntroductionIn sub-Saharan Africa, approximately 100 million people have CKD, yet genetic risk factors are not well-understood. Despite the potential importance of understanding APOL1 risk allele status among individuals with CKD, little genetic research has been conducted. Therefore, we conducted a pilot study evaluating the feasibility of and willingness to participate in genetic research on kidney disease, and we estimated APOL1 risk allele frequencies among individuals with CKD.MethodsIn 2014, we conducted a community-based field study evaluating CKD epidemiology in northern Tanzania. We assessed for CKD using urine albumin and serum creatinine to estimate GFR. We invited participants with CKD to enroll in an additional genetic study. We obtained dried-blood spots on filter cards, from which we extracted DNA using sterile punch biopsies. We genotyped for two single nucleotide polymorphisms (SNPs) defining the APOL1 G1 risk allele and an insertion/deletion polymorphism defining the G2 risk allele. Genotyping was performed in duplicate.ResultsWe enrolled 481 participant, 57 (12%) of whom had CKD. Among these, enrollment for genotyping was high (n = 48; 84%). We extracted a median of 19.4 ng of DNA from each dried-blood spot sample, and we genotyped the two APOL1 G1 SNPs and the APOL1 G2 polymorphism. Genotyping quality was high, with all duplicated samples showing perfect concordance. The frequency of APOL1 risk variants ranged from 7.0% to 11.0%, which was similar to previously-reported frequencies from the general population of northern Tanzania (p>0.2).DiscussionIn individuals with CKD from northern Tanzania, we demonstrated feasibility of genotyping APOL1 risk alleles. We successfully genotyped three risk variants from DNA extracted from filter cards, and we demonstrated a high enrollment for participation. In this population, more extensive genetic studies of kidney disease may be well-received and will be feasible.

Association of Genetic Polymorphisms of TGF-β1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV

“…5,29 In the Ethiopian study, none of the HIV-infected patients had the APOL1 G1 SNP, while the APOL1 G2 SNP was found (in the heterozygous state) in only 2 of 338 patients. The frequency of APOL1 renal risk variants was 9% to 11% in a study from East Africa, 28 and this value corresponds closely to many other studies in the region. In West Africa, some studies have documented one of the highest APOL1 renal risk variant frequencies, and this corresponds to SSA having the highest CKD prevalence on the continent.…”

“…Since the discovery of APOL1 genetic risk alleles among the African American population, there has been keen interest in determining the frequency and contribution of these risk alleles to the increasing CKD burden in SSA. The findings have been variable, ranging from the complete absence of APOL1 risk variants in Ethiopian populations 27 to intermediate prevalence in other Eastern African communities, 28 and then to the very high prevalence in West Africa. 5,29 In the Ethiopian study, none of the HIV-infected patients had the APOL1 G1 SNP, while the APOL1 G2 SNP was found (in the heterozygous state) in only 2 of 338 patients.…”

APOL1 Renal Risk Variants and Sickle Cell Trait Associations With Reduced Kidney Function in a Large Congolese Population-Based Study

“…Overall, our data and others from the DRC revealed much lower APOL1 risk genotype prevalence than compared with West African studies (G1, >40%; G2, 6%–24%), on which we based our power analysis to design our study. DRC APOL1 frequencies rather fitted within the range of East African studies (G1, 5%–11%; G2, 0%–5%), 12 , 36 , 38 , 39 which is consistent with the West-East decline of APOL1 G1 and, to a lesser extent, G2 allele frequency across the African continent.…”

How to estimate glomerular filtration rate in sub-Saharan Africa: design and methods of the African Research into Kidney Diseases (ARK) study

“…We will examine the role of traditional cardiovascular risk factors including diabetes mellitus, obesity and lipid profiles along with conventional and ambulatory blood pressure monitoring. In addition we will measure the impact of infections which may be of great importance in this region where infectious diseases are common and may play a major role in disease causation alongside genetic factors [43][44][45][46][47][48][49].…”