APOL1 CKD Risk Alleles in New Mexico African American and American Indian Populations: Racial Disparity

Purpose/Background: Two haplotypes of human apolipoprotein L1 gene (gene: APOL1; protein: ApoL1) harboring three coding sequence mutations have been demonstrated as risk variants associated with non-diabetic chronic kidney diseases (CKD) in African Americans. The first one, termed G1, is a two non-synonymous SNP haplotype (rs73885319 (A\u3eG; p.S342G) and rs60910145 (G\u3eT; p.I384M). The second one, termed G2, is a two codon deletion haplotype rs71785313 (6-bp in frame deletion) These two coding-sequence variants have been discovered in CKD patients of African ancestry and linked to the pathogenesis of primary focal and segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, and HIV-associated nephropathy (HIVAN), under a recessive inheritance pattern. Marked disparities exist in races, rates, and etiological classifications of CDK between African Americans (AAs) and European Americans. Sequencing and genotyping analysis of known APOL1 SNPs showed that only APOL1 G1 and G2 confer kidney risk, and other common and rare APOL1 missense variants, including the G3 haplotype, do not contribute to FSGS and HIVAN in the US population. According to the report of US census bureau, African American and American Indian (AI) citizens in New Mexico make up nearly 2.5% and 10.9% of the state\u27s entire population in 2018 (2). However, whether APOL1 G1 and G2 kidney-risk alleles are linked with hypertension-attributed CKD in AAs and AIs in New Mexico has not been investigated. Materials & Methods: We analyzed the published results of a retrospective analysis of inpatient and discharge data from hospitals across the state of New Mexico, known as Hospital Inpatient and Discharge Dataset (HIDD; 3). Results: A pattern persisted for all three years (2012-2014) that AAs had the highest rate of CKD followed by AIs per 10,000 population in New Mexico. AAs had the highest age adjusted rate of CKD with hypertension at 102.6 per 10,000 population (29.7% (102.6/345.7) of all CKD with hypertension patients) followed by American Indians at 91.9 (26.6% (91.9/345.7) of all CKD with hypertension patients). Interestingly, in terms of CKD with diabetes, AIs had the highest age adjusted rate at 79.9 per 10,000 followed by AAs at 66.5. Discussion/Conclusion: The prevalence of CKD with hypertension in AA and AI populations is significantly high in New Mexico, To understand the etiology of CKD in AAs and AIs in New Mexico, genotyping the APOL1 G1 and G2 risk alleles in these two populations is warranted. Detection of APOL1 associations with CKD and delineation of injury pathways (autophagy, necroptosis and ferroptosis) would bring hope for effective treatment for these kidney diseases. In addition, modifier loci can influence APOL1 risk for the development of CKD. ‘Second hits’, for example viral and environmental, may alter the outcome of APOL1 risk variants