Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions

Clinical course & management of childhood nephrotic syndrome in Germany: a large epidemiological ESPED study

Abstract Background Nephrotic syndrome (NS) is one of the most frequent occurring chronic kidney diseases in childhood, despite its rarely occurrence in the general population. Detailed information about clinical data of NS (e.g. average length of stay, complications) as well as of secondary nephrotic syndrome (SNS) is not well known. Methods A nationwide ESPED follow-up study presenting the clinical course and management of children with NS in Germany. Results In course of 2 years, 347 children developed the first onset of NS, hereof 326 patients (93.9%) had a primary NS, and 19 patients had a SNS (missing data in 2 cases), the majority due to a Henoch-Schönlein Purpura. Patients with steroid-resistant NS (SRNS) stayed significantly longer in hospital than children with steroid-sensitive NS (25.2 vs. 13.3 d, p <  0.001). Patients with bacterial/viral infections stayed longer in hospital (24.9 d/19.5d) than children without an infection (14.2 d/14.9 d; p <  0.001; p = 0.016). Additionally, children with urinary tract infections (UTI) (p < 0,001), arterial hypertension (AH) (p < 0.001) and acute renal failure (ARF) (p < 0,001) stayed significantly longer in hospital. Patients with SRNS had frequent complications (p = 0.004), such as bacterial infections (p = 0.013), AH (p < 0.001), UTI (p < 0.001) and ARF (p = 0.007). Children with a focal segmental glomerulosclerosis (FSGS) had significantly more complications (p = 0.04); specifically bacterial infections (p = 0.01), UTI (p = 0.003) and AH (p < 0,001). Steroid-resistance was more common in patients with UTI (p < 0.001) and in patients with ARF (p = 0.007). Furthermore, steroid-resistance (p < 0.001) and FSGS (p < 0.001) were more common in patients with AH. Conclusions This nationwide, largest German study presents results on the clinical course of children with NS considering a diverse range of complications that can occur with NS. The establishment of a region-wide and international pediatric NS register would be useful to conduct further diagnostic and therapy studies with the aim to reduce the complication rate and to improve the prognosis of NS, and to compare the data with international cohorts

Cerebrovascular function associated with fluid, not crystallized, abilities in older adults : a transcranial doppler study

The brain is dependent on the cerebrovascular system, particularly microvasculature, for a consistent blood supply; however, age-related changes in this system affect neuronal and therefore cognitive function. Structural vascular markers and vascular disease appear to preferentially affect fluid cognitive abilities, sparing crystallized abilities. We sought to investigate the relationships between cerebrovascular function and cognitive domains. Fifty individuals between 60 and 75 years of age (31 women, 19 men) underwent cognitive testing: Wechsler Vocabulary and Matrix Reasoning subtests (crystallized and fluid ability measures, respectively Wechsler, 2011), and the Addenbrooke's Cognitive Examination-Revised (ACE-R; general cognitive ability; Mioshi, Dawson, Mitchell, Arnold, & Hodges, 2006). Transcranial Doppler (TCD) measures were also collected at rest and during a cognitive word-generation task, from which a lateralization index was calculated. Lower pulsatility index at rest, and greater left lateralization during the TCD cognitive task were associated with better performance on the Matrix Reasoning but not the Vocabulary test; these effects were independent from each other and from any vascular comorbidity burden. These functional findings confirm previous structural studies, which revealed that fluid abilities are more vulnerable to cerebrovascular dysfunction than crystallized abilities, and identify two (likely related) mechanisms: degraded cerebrovascular integrity (indexed by pulsatility index) and a delateralization of function. Cerebrovascular dysfunction is a key contributor to cognitive aging that deserves further attention, particularly in relation to early diagnostic markers of impairment and monitoring of vascular (e.g., physical activity) interventions.11 page(s