PubMed · 16178100
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James Kingsland. Colour-coded cures.. https://pubmed.ncbi.nlm.nih.gov/16178100/
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BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
BACKGROUND: MSR1 has been reported to be associated with increased risk of prostate cancer (PCa). METHODS: We performed a meta-analysis of all eight published studies to evaluate the pooled effect of three rare mutations (R293X, S41T, and D174Y) and five common sequence variants (PRO3, INDEL1, IVS5-59, P275A, and INDEL7), stratified by race and sporadic/hereditary cancer. RESULTS: Several variants were significantly or marginally significantly associated with sporadic, not hereditary PCa risk, including R293X in white men (random effect OR = 1.34, P = 0.09) and D174Y in black men (random effect OR = 2.41, P = 0.04). The associations were not significant when the initial study was excluded. However, the frequency of the D174Y mutation was consistently higher among cases in all three studies that examined black men. CONCLUSIONS: Overall, this meta-analysis suggests the MSR1 gene does not independently confer a major risk to PCa but may confer a moderate risk to PCa, especially in black men.
Proposals on consent for research with biological samples should be informed by empirical studies of individuals' views. Studies to date queried mostly white research subjects. The aim of this study was to compare the views of two groups of patients: cancer patients at a university clinic (Winship Cancer Institute at Emory Healthcare) and cancer patients at an inner city county hospital (Grady) who were given the option of tissue banking. Overall, 315/452 (70%) patients completed the survey. The Grady cohort was 86% African American; the Winship cohort was 82% White. The vast majority (95%) of individuals in both cohorts agreed to provide a biological sample for future research. Both cohorts were willing for their samples to be used to study cancer and other diseases, including Alzheimer disease. Few participants preferred to control the disease to be studied (10%) or wished to be contacted again for consent for each future research project (11%). In our sample, almost all clinical patients, regardless of site of care, ethnicity or socioeconomic status, were willing to provide a biological sample for research purposes and allow investigators to determine the research to be done without contacting the patients again. These findings support the recommendation to offer individuals a simplified consent with a one-time binary choice whether to provide biological samples for future research.