Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5)

Glaciovolcanic hydrothermal environments in Iceland and implications for their detection on Mars

Volcanism has been a dominant process on Mars, along with a pervasive global cryosphere. Therefore, the interaction between these two is considered likely. Terrestrial glaciovolcanism produces distinctive lithologies and alteration terrains, as well as hydrothermal environments that can be inhabited by microorganisms. Here, we provide a framework for identifying evidence of such glaciovolcanic environments during future Mars exploration, and provide a descriptive reference for active hydrothermal environments to be utilised for future astrobiological studies. Remote sensing data were combined with field observations and sample analysis that included X-ray diffraction, Raman spectroscopy, thin section petrography, scanning electron microscopy, electron dispersive spectrometer analysis, and dissolved water chemistry to characterise samples from two areas of basaltic glaciovolcanism: Askja and Kverkfjöll volcanoes in Iceland. The glaciovolcanic terrain between these volcanoes is characterised by subglacially-erupted fissure swarm ridges, which have since been modified by multiple glacial outburst floods. Active hydrothermal environments at Kverkfjöll include hot springs, anoxic pools, glacial meltwater lakes, and sulfur- and iron- depositing fumaroles, all situated within ice-bound geothermal fields. Temperatures range from 0 °C - 94.4 °C, and aqueous environments are acidic - neutral (pH 2 - 7.5) and sulfate-dominated. Mineralogy of sediments, mineral crusts, and secondary deposits within basalts suggest two types of hydrothermal alteration: a low-temperature ( 120 °C) assemblage signified by zeolite (heulandite) and quartz. These mineral assemblages are consistent with those identified at the Martian surface. In-situ and laboratory VNIR (440 – 1000 nm) reflectance spectra representative of Mars rover multispectral imaging show sediment spectral profiles to be influenced by Fe2 +/3 + - bearing minerals, regardless of their dominant bulk mineralogy. Characterising these terrestrial glaciovolcanic deposits can help identify similar processes on Mars, as well as identifying palaeoenvironments that may once have supported and preserved life

Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Dawn de Vere, Summertown, South Australia, ca. 1975, 2 [picture] /

Dawn was a costume maker inspired by the medieval era.; Part of: Sheilas, a tribute to Australian women collection, ca. 1975.; Title devised by cataloguer based on information supplied by photographer.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn4227597

The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldParathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64 degrees N), where daily intake of cod liver oil is common and mean calcium intake is high. In PTH correlated inversely with 25(OH)D (r = -0.26, p<0.0 1). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R2 = 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis

Is blood pressure commonly raised by moderate consumption of liquorice?

It is well known that excessive liquorice intake can induce sodium and fluid retention, hypokalaemia, hypertension and inhibition of the renin-angiotensin system. We tested whether regular moderate liquorice consumption (50 g and 100 g daily) raises blood pressure (BP) in a normotensive population. Ingestion of 100 g of liquorice daily (n = 30) caused a significant rise in systolic blood pressure (SBP) by a mean of 6.5 mm Hg (P < 0.001) and a fall in plasma potassium by 0.24 mmol/l (P < 0.001); the highest rise in SBP observed was 19 mm Hg. In a subgroup of 13 women the consumption of 50 g of liquorice daily also caused a significant rise in SBP of 5.6 mm Hg (P < 0.001) and DBP of 3.4 mm Hg (P = 0.002). A significant change in the cortisol/cortisone ratio in urine was observed during 100 g liquorice consumption indicating inhibition of 11 beta-hydroxysteroid dehydrogenase in kidneys. The results indicate that liquorice-induced hypertension might be more common than has been appreciated and it important for medical doctors to be on the alert for this effect in both the prevention and treatment of hypertension

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVES: The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. DESIGN: This was a cross-sectional study consisting of 516 healthy men and women, aged 30-85, all Caucasians with vitamin D insufficiency [serum 25(OH)D<45 nmol L(-1)]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately. RESULTS: We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin-like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R(2)=0.472) but smoking, BMI and kidney function in women (R(2)=0.362). CONCLUSIONS: Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women

Serum 25-hydroxyvitamin D levels and bone mineral density in 16-20 years-old girls: lack of association.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Hypovitaminosis D has been shown to be associated with low bone mineral density in middle-aged and elderly women. The aim of this study was to evaluate whether such an association might exist in adolescent and young adult girls, approaching peak bone mass. DESIGN: Cross-sectional study carried out in late winter. SETTING: Reykjavik area at latitude 64 degrees N. SUBJECTS: Two-hundred and fifty-nine Icelandic Caucasian girls, aged 16, 18 and 20 years, randomly selected from the registry of Reykjavik. MAIN OUTCOME MEASURES: Bone mineral density in lumbar spine, hip, distal forearm and total skeleton was measured with dual-energy X-ray absorptiometry (DEXA) and compared with 25-hydroxyvitamin D levels [25 (OH)D] in serum, measured by radioimmunoassay. Calcium and vitamin-D intake were also assessed by a questionnaire. RESULTS: 18.5% of the girls were below 25 nmol L-1 in serum 25 (OH)D which has been recognized as the lower normal limit for adults. No significant association was found between 25 (OH)D levels and bone mineral density. CONCLUSIONS: Normal calcium and phosphate concentrations in plasma and normal bone mineral density are maintained in adolescent and young adult girls at lower 25 (OH)D levels than published 'normal' levels for middle-aged and elderly