Healthcare Barriers of Residents at a Subsidized Housing Community

Introduction: Despite expanded healthcare programs, the low income and elderly lack coverage of vision, hearing, and dental services. Community services are often asked to fill these gaps. To evaluate the situation in Burlington, VT, we surveyed staff and residents in Burlington Housing Authority (BHA) subsidized housing to (1) identify gaps in healthcare coverage and (2) assess barriers to accessing those services in this population.https://scholarworks.uvm.edu/comphp_gallery/1207/thumbnail.jp

APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor) and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of these alleles, but when homozygous the G1 and G2 alleles predispose to glomerulosclerosis. While efforts are underway to screen patients for G1 and G2 alleles and to better understand "APOL1 glomerulopathy," no data prove that these APOL1 sequence variants cause glomerulosclerosis. G1 and G2 correlate best with glomerulosclerosis as recessive alleles, which suggests a loss of function mutation for which proof of causality is commonly tested with homozygous null alleles. This test cannot be performed in rodents as the APOL gene cluster evolved only in primates. However, there is a homozygous APOL1 null human being who lives in a village in rural India. This individual and his family offer a unique opportunity to test causality between APOL1 null alleles and glomerulosclerosis.We obtained clinical data, blood and urine from this APOL1 null patient and 50 related villagers. Based on measurements of blood pressure, BUN, creatinine, albuminuria, genotyping and immunoblotting, this APOL1 null individual does not have glomerulosclerosis, nor do his relatives who carry APOL1 null alleles.This small study cannot provide definitive conclusions but the absence of glomerulosclerosis in this unique population is consistent with the possibility that African-American glomerulosclerosis is caused, not by loss of APOL1 function, but by other mechanisms including a subtle gain of function or by the "genetic hitchhiking" of deleterious mutations in a gene linked to APOL1 G1 and G2

Clinical Data.

<p>From 51 subjects, clinical data for blood pressure, serum BUN, serum creatinine, and urine albumin∶creatinine ratios were sorted by genotype for comparison: “null” = homozygous null (N = 1); “het” = heterozygote (N = 8); “w.t.” = wild type (N = 42). Error bars represent S.D.</p

Model of “Genetic Hitchhiking” at the <i>MYH9</i>/<i>APOL1</i> locus.

<p>All genes at the locus (blue lines, top) are not depicted. The G1 and G2 <i>APOL1</i> polymorphisms (green circle) undergo positive selection over time due to increased resistance against Trypanosoma, eventually reaching high allele frequency. In the process, other nearby polymorphisms “hitchhike” along with G1 and G2, including intronic polymorphisms in <i>MYH9</i> (orange box), and hypothesized “glomerulosclerosis polymorphisms” in linked disease genes that have not been identified. The number of such “glomerulosclerosis polymorphisms” and the number of genes involved (1 or several) is not known. For the purposes of this cartoon we depict three hitchhiking polymorphisms (Xs of different colors) in a disease gene on one side of <i>APOL1</i>, and 1 polymorphism (Y) in a second disease gene on the other side of <i>APOL1</i>. We hypothesize that each individual “glomerulosclerosis polymorphism” is present at low frequency and has escaped statistical significance within the cohorts that have been examined, but in aggregate, multiple “glomerulosclerosis polymorphisms” that hitchhiked along with <i>APOL1</i> may account fully for disease. Possible methods of identifying such glomerulosclerosis polymorphisms are proposed in the Discussion. This hypothesis of multiple, rare polymorphisms that hitchhike along with G1 and G2 could explain why <i>APOL1</i> correlates highly with glomerulosclerosis and yet only ∼5% of G1/G2 homozygous individuals develop glomerulosclerosis (those 5% of G1/G2 persons who are also homozygous for the hitchhiking “glomerulosclerosis polymorphisms”). Lastly, we make no assumptions about the evolution of these causal “glomerulosclerosis polymorphisms,” which may have been present in <i>cis</i> to G1/G2 before a selective sweep (red and blue X, red Y), or may have arisen during or late in the process of positive selection for G1/G2 (green X). Two recombination events are depicted, and while neither is informative, recombination breakpoints of uncommon HIVAN or FSGS patients who do not have 2 alleles of G1/G2 may be highly informative (see Discussion).</p

<i>APOL1</i> null alleles in 51 participants.

<p>(A) PCR products that span alleles A and B were amplified from participant genomic DNA and yielded a product of the expected size. Lane M = 5 uL Quickload PCR marker. Lanes 1–12 used the same master mix. Lane 1 is water control and lanes 2–12 have 100 ng genomic DNA from different participants. (B) Sanger sequencing identified alleles A and B. Purified PCR products were sequenced with nested internal primers. Sequence tracings are shown for instances in which allele A or allele B was detected. As shown, signal interpretation is clear until the site of the deletion, after which the tracing shows a mixture of two signals. Half of the signal is from the wild type allele, with the expected nucleotide as shown below, and half the signal is from the nucleotide offset by either 1 nt (allele A) or 2 nts (allele B). Additional tracings are available in supplemental data (C) Immunoblots of serum from all 51 participants were probed with α-APOL1. Loading controls used α-albumin as shown or α-transferrin (not shown). M = marker. Lanes 1–8 are participant serum, with a doublet of ∼41/39 kDa observed in all lanes except one, which corresponds to the null patient. These blots were confirmed in triplicate.</p

The inheritance of alleles A and B are depicted within a family dendogram, which also illustrates salient clinical findings.

<p>Other study participants not depicted in this dendogram were wild type for both <i>APOL1</i> null alleles and were not part of the immediate family.</p