Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Analysis of Titin in Red and White Muscles: Crucial Role on Muscle Contractions Using a Fish Model

Several studies have compared molecular components between red and white skeletal muscles in mammals. However, mammalian skeletal muscles are composed of mixed types of muscle fibers. In the current study, we analyzed and compared the distributions of titin, lipid, phosphate ions, and fatty acid levels in red and white muscles using a fish model (Tilapia), which is rich in red and white muscles, and these are well separated. Oil-red O staining showed that red muscle had more-abundant lipids than did white muscle. A time-of-flight secondary-ion mass spectrometric (TOF-SIMS) analysis revealed that red muscle possessed high levels of palmitic acid and oleic acid, but white muscle contained more phosphate ions. Moreover, elastica-van Gieson (EVG) and Mito-Tracker green FM staining showed that collagen and elastic fibers were highly, respectively, distributed in connective tissues and mitochondria in red muscle. An electron micrographic analysis indicated that red muscle had a relatively higher number of mitochondria and longer sarcomere lengths and Z-line widths, while myofibril diameters were thicker in white muscle. Myofibrillar proteins separated by SDS-PAGE showed that the major giant protein, titin, was highly expressed in white muscle than in red muscle. Furthermore, ratios of titin to myosin heavy chain (MHC) (titin/MHC) were about 1.3 times higher in white muscle than red muscle. We postulated that white muscle is fit for short and strong contractile performance due to high levels of titin and condensed sarcomeres, whereas red muscle is fit for low intensity and long-lasting activity due to high levels of lipids and mitochondria and long sarcomeres

Dengue Fever Scoring System: New Strategy for the Early Detection of Acute Dengue Virus Infection in Taiwan

Dengue fever is an important public health problem in Southern Taiwan. The purpose of this study was to develop a dengue scoring system using a three-stage process, which may be used as a guidance tool for the early diagnosis of dengue fever. Methods: A retrospective study was conducted to identify factors useful for the early diagnosis of dengue fever. We assessed the clinical and laboratory features of 89 adult patients with dengue from 2002 to 2004 at a community-based hospital. They were compared with 14 patients with scrub typhus, 104 with Q fever, and 35 with murine typhus, which might present similar symptoms and signs as dengue infection. A scoring system was designed after analysis of the retrospective study and with the assistance of 10 expert clinicians. For the second stage, we evaluated efficiency in differentiating dengue fever from Q fever, scrub typhus and murine typhus in three hospitals from 2002 to 2005. For the third stage, we prospectively used the dengue scoring system for 498 cases that clinically were suspected as having dengue infection in the city of Kaohsiung from January 2006 to September 2006. Results: The performance of the scoring system was 88.1% sensitivity, 94.9% specificity, 95.7% positive predictive value (PPV), and 86.1% negative predictive value (NPV). Evaluation of the scoring system at the third stage revealed 90.7% sensitivity, 86.9% specificity, 81.4% PPV, and 93.6% NPV. Conclusion: The dengue scoring system had a high NPV that might be helpful in the early diagnosis of dengue fever in adults before laboratory data are available