New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America

Background:Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediateStaphylococcus aureus(hVISA) phenotype is associated with therapeutic failure. However, hVISAisolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures.Objectives:To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine LatinAmerican countries.Methods:We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection ofhVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjectedto population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogatedalterations in predicted proteins associated with the development of the VISA phenotype in both hVISA andvancomycin-susceptibleS. aureus(VSSA) genomes.Results:A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off(0.9). The majority of the 39 hVISA isolates exhibited the Leu-14!Ile (90%) and VraT Glu-156!Gly (90%) aminoacid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involvingWalK, VraS, RpoB and RpoC proteins.Conclusions:The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteinsinvolved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest thatEtest-based methods are an important alternative for the detection of hVISA clinical isolates