Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population.

INTRODUCTION: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. METHODS: Nondiabetic individuals aged 30-70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. RESULTS: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10-6), TMEM161 (p = 4.43 × 10-6), EFCAB1 (p = 2.03 × 10-6), ELMOD1 (p = 2.97 × 10-6), RYR3 (p = 1.34 × 10-6), and PIEZO2 (p = 2.19 × 10-7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10-6 and 5 × 10-5 are also identified in five genes that may have a biological role in the development of albuminuria. CONCLUSION: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.

A genome-wide association study for melatonin secretion.

Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10-7 to 3.44 × 10-6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

Herpes simplex virus-1 induces expression of a novel MxA isoform that enhances viral replication.

MxA is an antiviral protein induced by interferon (IFN)-α/ß that is known to inhibit the replication of many RNA viruses. In these experiments, the 76-kDa MxA protein expressed in IFN-α-treated cells was shown to have antiviral activity against herpes simplex virus-1 (HSV-1), a human DNA virus. However, MxA was expressed as a 56-kDa protein in HSV-1-infected cells in the absence of IFN-α. This previously unrecognized MxA isoform was produced from an alternatively spliced MxA transcript that had a deletion of Exons 14-16 and a frame shift altering the C-terminus. The variant MxA (varMxA) isoform was associated with HSV-1 regulatory proteins and virions in nuclear replication compartments. varMxA expression enhanced HSV-1 infection as shown by a reduction in infectious virus titers from cells in which MxA had been inhibited by RNA interference and by an increase in HSV-1 titers when the 56-kDa varMxA was expressed constitutively. Thus, the human MxA gene encodes two MxA isoforms, which are expressed differentially depending on whether the stimulus is IFN-α or HSV-1. These findings show that alternative splicing of cellular mRNA can result in expression of a novel isoform of a host defense gene that supports instead of restricting viral infection.

Filtration of dust particulates with a moving granular bed filter.

The goal of this study was to evaluate the performance of a moving granular bed filter designed for cold test to filter coal particulates. A series of experiments were carried out at room temperature to demonstrate the collection efficiency of this method of filtration technology (i.e., the moving granular bed filter) at different filtration superficial velocities and mass flow rates of filter granules but with a fixed inlet dust concentration. The dynamic characteristics of the filter system were evaluated by measuring variations in the outlet concentration and size distribution of dust particulates. The collection mechanisms of the filter granules in the moving granular bed filter were also studied. Experimental results showed that the collection efficiency could be enhanced by using a filtration superficial velocity of 30 cm/s and mass flow rate of 450 g/min. The results of this study indicate this type of method could be useful for application in different cross-flow filter systems for gas cleanup. The focus in the current study is essentially the development of a moving granular bed filter that could be applied in a high-temperature environment. The results are expected to serve as the basis for future research.