PubMed · 5975655
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M Douglas. 1966. Population control in primitive groups.. https://pubmed.ncbi.nlm.nih.gov/5975655/
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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.
To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.m(2)/cm(5), p <0.01) and a lower cardiac index (2.64 +/- 0.73 vs 3.10 +/- 0.71 L/min.m(2), p <0.01) than premenopausal women. Postmenopausal women also had less nocturnal decreases in both systolic (15 +/- 8 vs 19 +/- 8 mm Hg, p <0.01) and diastolic (12 +/- 6 vs 15 +/- 6 mm Hg, p = 0.05) pressures during ambulatory monitoring and higher levels of hematocrit (40 +/- 2% vs 38 +/- 3%, p <0.01). In association with this greater hemodynamic load, postmenopausal women had evidence of early concentric left ventricular remodeling, manifested by a greater relative wall thickness (0.38 +/- 0.06 vs 0.35 +/- 0.06, p <0.01) than that observed in premenopausal women. Differences between pre- and postmenopausal women in hemodynamics, diurnal blood pressure variation, and left ventricular structure were observed in white and African-American subjects. These results suggest that menopause is associated with hemodynamic changes and left ventricular remodeling, which may contribute to the enhanced cardiovascular risk observed in postmenopausal women.
The relation between birth characteristics and leukemia in young children was investigated in a large population-based study in California. Cases were obtained from the statewide cancer registry for 1988-1997. During this time, 1,957 leukemia cases were diagnosed among children under age 5 years. Of these, 1,728 (88%) were matched to a California birth certificate. Two control birth certificates, matched on date of birth and sex, were randomly selected from the statewide birth registry for each case. Analyses were performed separately for acute lymphoid leukemia (ALL) and acute nonlymphoid leukemia (ANLL). Odds ratios and 95% confidence intervals were estimated from conditional logistic regression. The strongest finding was for greatly increased risk of both types of leukemia in children with Down's syndrome (22 cases and no controls). African-American children had strikingly decreased risk for ALL (odds ratio (OR) = 0.29, 95% confidence interval (CI): 0.20, 0.42), and Asian/Pacific Islanders had increased risk for ANLL (OR = 2.00, 95% CI: 1.19, 3.36). Older maternal age was associated with slightly increased risk for ALL (maternal age > or =35 years, OR = 1.25, 95% CI: 1.04, 1.52), although this odds ratio was somewhat reduced when adjusted for other factors. No strong relations were observed for birth weight and ALL or ANLL.