PubMed · 3852700
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M J Viljoen, J C Venter. 1985. A community development project.. https://doi.org/10.4102/curationis.v8i3.608
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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.
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BACKGROUND: Studies have shown that the birth weight of infants is correlated with the birth weights of their siblings and their mothers. We investigated whether the birth weights of mothers and index children were jointly associated with the risk of low birth weight in the siblings of the index children. METHODS: We used data on the live-birth cohort of the 1988 National Maternal and Infant Health Survey. The analysis included 1691 white and 1461 black mothers, each of whom had two or more live-born, singleton children. Multiple logistic regression with generalized-estimation equations was used to assess the risk of low birth weight among an index child's siblings. Four groups were studied: that in which neither the mother nor the index child had low birth weight (group 1), that in which only the mother had low birth weight (group 2), that in which only the index child had low birth weight (group 3), and that in which both the mother and the index child had low birth weight (group 4). There was adjustment for other maternal and infant covariates. RESULTS: Among white siblings in groups 1, 2, 3, and 4, 3.6, 8.3, 21.2, and 38.9 percent, respectively, had low birth weight, as compared with 8.0, 19.0, 31.1, and 57.1 percent of black siblings. When group 1 was used as the reference group, the adjusted odds ratios (and 95 percent confidence intervals) for low birth weight in groups 2, 3, and 4 were 2.5 (1.4 to 4.3), 6.8 (4.7 to 9.8), and 15.4 (9.2 to 25.5), respectively, among white siblings and 2.6 (1.8 to 3.8), 4.7 (3.5 to 6.4), and 13.9 (9.2 to 20.9) among black siblings. These associations were consistently found for birth weights below 1500 g and those ranging from 1500 to 2499 g in both races and after stratification for the mother's age, parity, education, cigarette-smoking status, and weight and height before pregnancy and the infant's sex. CONCLUSIONS: Although selection and recall biases cannot be excluded with certainty, our data suggest a strong familial aggregation of low birth weight among both whites and blacks in the United States.