Human Uromodulin ELISA Kit

The viability of using NIST610 glass as an external standard for allanite U-Th-Pb geochronology by 193 nm laser ablation inductively-coupled plasma mass spectrometry was investigated. Laser ablation conditions were optimized to minimize time-dependent fractionation of Pb/U and Pb/Th. A data reduction scheme (VizualAge_UMod) was additionally used to apply Pb/U fractionation corrections when the standard contains an enriched U-238/U-235 ratio (NIST610 = 420) compared to natural materials. Optimization of ablation conditions was carried out on natural allanite material separated from a similar to 415 Ma tonalite intrusion (Hartfield intrusion, New Brunswick Canada). Conditions of 25 s of ablations at 1 J/cm(2), 3 Hz, and a 45 pm crater diameter were established. This produced 3 pm deep craters, and a near-steady-state, low mass-load, material transfer to the ICP-MS producing negligible time-dependent Pb/U and Pb/Th fractionation. Increasing fluence only modestly up to 3 J/cm(2) induced time-dependent Pb/U fractionation. To test for any residual matrix dependencies, the long-term reproducibility, accuracy, and absolute precision of the method was verified using similar to 31.5 Ma Siss3 allanite material (Bergell Intrusion, Switzerland). The method yielded accurate and precise Pb/U ad Pb/Th ages that compare favourably to alternative allanite dating methods. As a further test, allanite separated from the Hartfield tonalite was analyzed and yielded an age that overlaps within error of the TIMS titanite U-Pb age for the intrusion. This is despite a partially amorphous microstructure as documented by Raman spectroscopy and optical microscopy. The results of this study emphasize the need to empirically calibrate laser fluence conditions that yield minimal element fractionation and to establish robust plasma settings. These conditions are unlikely to yield highest sensitivity, but should minimize the effects of the numerous laser-induced and plasma ionization processes that lead to Pb/U fractionation. (C) 2016 Elsevier B.V. All rights reserved.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.