17 research outputs found

    A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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    dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

    Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L

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    The Cockcroft-Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p<0.0001) was found between cystatin C and iohexol clearance (r(2) =0.91) than between creatinine and iohexol clearance (r(2) =0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y=77.24x -1.2623 (Dade Behring cystatin C calibration) or y=99.43x -1.5837 (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations

    Carbon dioxide level and form of soil nitrogen regulate assimilation of atmospheric ammonia in young trees

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    The influence of carbon dioxide (CO(2)) and soil fertility on the physiological performance of plants has been extensively studied, but their combined effect is notoriously difficult to predict. Using Coffea arabica as a model tree species, we observed an additive effect on growth, by which aboveground productivity was highest under elevated CO(2) and ammonium fertilization, while nitrate fertilization favored greater belowground biomass allocation regardless of CO(2) concentration. A pulse of labelled gases ((13)CO(2) and (15)NH(3)) was administered to these trees as a means to determine the legacy effect of CO(2) level and soil nitrogen form on foliar gas uptake and translocation. Surprisingly, trees with the largest aboveground biomass assimilated significantly less NH(3) than the smaller trees. This was partly explained by declines in stomatal conductance in plants grown under elevated CO(2). However, unlike the (13)CO(2) pulse, assimilation and transport of the (15)NH(3) pulse to shoots and roots varied as a function of interactions between stomatal conductance and direct plant response to the form of soil nitrogen, observed as differences in tissue nitrogen content and biomass allocation. Nitrogen form is therefore an intrinsic component of physiological responses to atmospheric change, including assimilation of gaseous nitrogen as influenced by plant growth history
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