APOL1
Apolipoprotein L1 precursor (Apolipoprotein L) (Apo-L) (ApoL) (Apolipoprotein L-I) (ApoL-I) [APOL]
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APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.
MeSH Terms
- Adolescent
- Adult
- African Americans
- Age Factors
- Aged
- Aging
- Alleles
- Apolipoprotein L1
- Apolipoproteins
- Body Mass Index
- Female
- Genotype
- Humans
- Kidney Glomerulus
- Lipoproteins, HDL
- Male
- Middle Aged
- Organ Size
- Young Adult
Keywords
- APOL1 risk alleles
- African Americans
- glomerular enlargement
- glomerular number
The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown. Among 462 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, we examined the cross-sectional association between apolipoprotein L1 (APOL1) risk variants and income with: 1) mildly reduced eGFR (<75 mL/min/1.73 m(2), creatinine-cystatin C equation) and 2) elevated urine albumin-to-creatinine ratio (ACR) (≥17 in men and ≥25 mg/g in women). High risk APOL1 status was defined by 2 copies of high-risk variants; low risk if 0 or 1 copy. Income groups were dichotomized as < $14,000/year (lowest income group) or ≥ $14,000/year. Logistic regression models were adjusted for age, sex, and % European ancestry. Overall, participants' mean age was 47 years and 16% (n = 73) had high risk APOL1 status. Mean eGFR was 99 mL/min/1.73 m(2). Mildly reduced eGFR was prevalent among 11% (n = 51). The lowest income group had higher adjusted odds (aOR) of mildly reduced eGFR than the higher income group (aOR 1.8, 95% CI 1.2-2.7). High-risk APOL1 was not significantly associated with reduced eGFR (aOR 1.5, 95% CI 0.9-2.5). Among 301 participants with ACR data, 7% (n = 21) had elevated ACR. Compared to low-risk, persons with high-risk APOL1 had higher odds of elevated ACR (aOR 3.8, 95% CI 2.0-7.3). Income was not significantly associated with elevated ACR (aOR 1.8, 95% CI 0.7-4.5). There were no significant interactions between APOL1 and income. Both genetic and socioeconomic factors may be important determinants of early kidney damage among AAs.
MeSH Terms
- African Americans
- Age Factors
- Aged
- Aging
- Albuminuria
- Apolipoprotein A-I
- Creatinine
- Cross-Sectional Studies
- Databases, Factual
- Environment
- Female
- Genetic Predisposition to Disease
- Geriatric Assessment
- Glomerular Filtration Rate
- Humans
- Income
- Logistic Models
- Male
- Middle Aged
- Prognosis
- Renal Insufficiency, Chronic
- Risk Assessment
- Sex Factors
- Socioeconomic Factors