Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) has been linked to various neurological complications. This meta-analysis assessed the relationship between glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in the blood and neurological injury in COVID-19 patients. A comprehensive search of various databases was conducted until 18 August 2023, to find studies reporting GFAP and NfL blood levels in COVID-19 patients with neurological complications. GFAP and NfL levels were estimated between COVID-19 patients and healthy controls, and meta-analyses were performed using RevMan 5.4 software for analysis. In the 21 collected studies, it was found that COVID-19 patients had significantly higher levels of pooled GFAP (SMD = 0.52; 95% CI: 0.31, 0.73; p ≤ 0.001) and NfL (SMD = 0.60; 95% CI: 0.37, 0.82; p ≤ 0.001) when compared to the healthy controls. The pooled GFAP (SMD = 0.86; 95% CI: 0.26, 1.45; p ≤ 0.01) and NfL (SMD = 0.87; 95% CI: 0.48, 1.26; p ≤ 0.001) were significantly higher in non-survivors. These findings indicate a significant association between COVID-19 severity and elevated levels of GFAP and NfL, suggesting that GFAP and NfL could serve as potential diagnostic and prognostic markers for the early detection and monitoring of COVID-19-related neurological injuries.

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation.

The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.

Artificial Intelligence-Assisted Diagnostic Cytology and Genomic Testing for Hematologic Disorders.

Artificial intelligence (AI) is a rapidly evolving field of computer science that involves the development of computational programs that can mimic human intelligence. In particular, machine learning and deep learning models have enabled the identification and grouping of patterns within data, leading to the development of AI systems that have been applied in various areas of hematology, including digital pathology, alpha thalassemia patient screening, cytogenetics, immunophenotyping, and sequencing. These AI-assisted methods have shown promise in improving diagnostic accuracy and efficiency, identifying novel biomarkers, and predicting treatment outcomes. However, limitations such as limited databases, lack of validation and standardization, systematic errors, and bias prevent AI from completely replacing manual diagnosis in hematology. In addition, the processing of large amounts of patient data and personal information by AI poses potential data privacy issues, necessitating the development of regulations to evaluate AI systems and address ethical concerns in clinical AI systems. Nonetheless, with continued research and development, AI has the potential to revolutionize the field of hematology and improve patient outcomes. To fully realize this potential, however, the challenges facing AI in hematology must be addressed and overcome.

Amine-Functionalized Quantum Dots as a Universal Fluorescent Nanoprobe for a One-Step Loop-Mediated Isothermal Amplification Assay with Single-Copy Sensitivity.

Loop-mediated isothermal amplification (LAMP) has received considerable attention for decentralized (point-of-care and on-site) nucleic acid testing in view of its simple temperature control (60-65 °C) and short assay time (15-60 min). There remains a challenge in its wide adoption and acceptance due to the limitations of the existing amplification result reporter probes, e.g., photobleaching of organic fluorophore and reduced sensitivity of the pH-sensitive colorimetric dye. Herein, we demonstrate CdSeS/ZnS quantum dots (semiconductor fluorescent nanocrystals with superior photostability than organic fluorophore) with surface modification of cysteamine (amine-QDs) as a new reporter probe for LAMP that enabled single-copy sensitivity (limit of detection of 83 zM; 20 µL reaction volume). For a negative LAMP sample (absence of target sequence), positively charged amine-QDs remained dispersed due to interparticle electrostatic repulsion. While for a positive LAMP sample (presence of target sequence), amine-QDs became precipitated. The characterization data showed that amine-QDs were embedded in magnesium pyrophosphate crystals (generated during positive LAMP), thus leading to their coprecipitation. This amine-QD-based one-step LAMP assay advances the field of QD-based nucleic acid amplification assays in two aspects: (1) compatibility─one-step amplification and detection (versus separation of amplification and detection steps); and (2) universality─the same amine-QDs for different target sequences (versus different oligonucleotide-modified QDs for different target sequences).

Transcriptional profiling of the chick retina identifies down-regulation of VIP and UTS2B genes during early lens-induced myopia.

Gene expression of the chick retina was examined during the early development of lens-induced myopia (LIM) using whole transcriptome sequencing. Monocular treatment of the right eyes with -10 diopter (D) lenses was performed on newly born chicks for one day (LIM-24) or two days (LIM-48), while the contralateral eyes without lenses served as controls. Myopia development was confirmed by demonstrating significant elongation of the optical axis in lens-treated eyes compared to untreated control eyes. RNA was extracted and RNA-seq was performed using the Illumina HiSeqTM 2000 platform. Data analysis was carried out on a Partek® Flow platform. Using screening criteria of ≥1.30-fold change and a false discovery rate <1%, 11 (five down-regulated and six up-regulated) and 35 differentially expressed genes (six down-regulated and twenty-nine up-regulated) were identified at 24 hours and 48 hours, respectively. Using another cohort for validation, Quantitative PCR confirmed significant changes in the expression of VIP and UTS2B mRNA (P <0.05) after only 24 hours of LIM treatment and numerical changes in the expression for PCGF5 and FOXG1, which were consistent with transcriptome sequencing but did not reach statistical significance. These data suggest that concerted changes of retinal gene expression may be instrumental in the initiation of axial elongation and myopia development.

Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules.

Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of better prevention and treatment strategies, including vaccines. Immune dysregulation due to pro-inflammatory mediators has worsened the situation in COVID-19 patients. Inflammasomes play a critical role in modulating pro-inflammatory cytokines in the pathogenesis of COVID-19 and their activation is associated with poor clinical outcomes. Numerous preclinical and clinical trials for COVID-19 treatment using different approaches are currently underway. Targeting different inflammasomes to reduce the cytokine storm, and its associated complications, in COVID-19 patients is a new area of research. Non-coding RNAs, targeting inflammasome activation, may serve as an effective treatment strategy. However, the efficacy of these therapeutic agents is highly dependent on the delivery system. MicroRNAs and long non-coding RNAs, in conjunction with an efficient delivery vehicle, present a potential strategy for regulating NLRP3 activity through various RNA interference (RNAi) mechanisms. In this regard, the use of nanomaterials and other vehicle types for the delivery of RNAi-based therapeutic molecules for COVID-19 may serve as a novel approach for enhancing drug efficacy. The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19.

Viral MicroRNAs Encoded by Nucleocapsid Gene of SARS-CoV-2 Are Detected during Infection, and Targeting Metabolic Pathways in Host Cells.

MicroRNAs (miRNAs) are critical regulators of gene expression that may be used to identify the pathological pathways influenced by disease and cellular interactions. Viral miRNAs (v-miRNAs) encoded by both DNA and RNA viruses induce immune dysregulation, virus production, and disease pathogenesis. Given the absence of effective treatment and the prevalence of highly infective SARS-CoV-2 strains, improved understanding of viral-associated miRNAs could provide novel mechanistic insights into the pathogenesis of COVID-19. In this study, SARS-CoV-2 v-miRNAs were identified by deep sequencing in infected Calu-3 and Vero E6 cell lines. Among the ~0.1% small RNA sequences mapped to the SARS-CoV-2 genome, the top ten SARS-CoV-2 v-miRNAs (including three encoded by the N gene; v-miRNA-N) were selected. After initial screening of conserved v-miRNA-N-28612, which was identified in both SARS-CoV and SARS-CoV-2, its expression was shown to be positively associated with viral load in COVID-19 patients. Further in silico analysis and synthetic-mimic transfection of validated SARS-CoV-2 v-miRNAs revealed novel functional targets and associations with mechanisms of cellular metabolism and biosynthesis. Our findings support the development of v-miRNA-based biomarkers and therapeutic strategies based on improved understanding of the pathophysiology of COVID-19.

The Tyrosine Kinase-Driven Networks of Novel Long Non-coding RNAs and Their Molecular Targets in Myeloproliferative Neoplasms.

Recent research has focused on the mechanisms by which long non-coding RNAs (lncRNAs) modulate diverse cellular processes such as tumorigenesis. However, the functional characteristics of these non-coding elements in the genome are poorly understood at present. In this study, we have explored several mechanisms that involve the novel lncRNA and microRNA (miRNA) axis participating in modulation of drug response and the tumor microenvironment of myeloproliferative neoplasms (MPNs). We identified novel lncRNAs via mRNA sequencing that was applied to leukemic cell lines derived from BCR-ABL1-positive and JAK2-mutant MPNs under treatment with therapeutic tyrosine kinase inhibitors (TKI). The expression and sequence of novel LNC000093 were further validated in both leukemic cells and normal primary and pluripotent cells isolated from human blood, including samples from patients with chronic myelogenous leukemia (CML). Downregulation of LNC000093 was validated in TKI-resistant CML while a converse expression pattern was observed in blood cells isolated from TKI-sensitive CML cases. In addition to BCR-ABL1-positive CML cells, the driver mutation JAK2-V617F-regulated lncRNA BANCR axis was further identified in BCR-ABL1-negative MPNs. Further genome-wide validation using MPN patient specimens identified 23 unique copy number variants including the 7 differentially expressed lncRNAs from our database. The newly identified LNC000093 served as a competitive endogenous RNA for miR-675-5p and reversed the imatinib resistance in CML cells through regulating RUNX1 expression. The extrinsic function of LNC000093 in exosomal H19/miR-675-induced modulation for the microenvironment was also determined with significant effect on VEGF expression.

Computer-assisted ultrasound assessment of plaque characteristics in radiation-induced and non-radiation-induced carotid atherosclerosis.

BACKGROUND: This study investigated the feasibility of using a computer-assisted method to evaluate and differentiate the carotid plaque characteristics in radiation-induced and non-radiation-induced carotid atherosclerosis. METHODS: This study included 107 post-radiotherapy (post-RT) nasopharyngeal carcinoma (NPC) patients and 110 subjects with cardiovascular risk factors (CVRFs). Each participant had a carotid ultrasound examination, and carotid plaques and carotid intima-media thickness (CIMT) were evaluated with grey scale ultrasound. The carotid plaque characteristics were evaluated for grey-scale median (GSM) and detailed plaque texture analysis (DPTA) using specific computer software. In DPTA, five different intra-plaque components were colour-coded according to different grey scale ranges. A multivariate linear regression model was used to evaluate the correlation of risk factors and carotid plaque characteristics. RESULTS: Post-RT NPC patients have significantly higher CIMT (748±15.1 µm, P=0.001), more patients had a plaque formation (80.4%, P<0.001) and more plaque locations (2.3±0.2, P<0.001) than CVRF subjects (680.4±10.0 µm, 38.2% and 0.5±0.1 respectively). Among the five intra-plaque components, radiation-induced carotid plaques had significantly larger area of calcification (4.8%±7.7%, P=0.012), but lesser area of lipid (42.1%±16.9%, P=0.034) when compared to non-radiation-induced carotid plaques (3.0%±5.7% and 46.3%±17.9% respectively). Age, radiation and number of CVRF were significantly associated with the carotid atherosclerosis burden (P<0.001). Besides, age was significantly associated with the amount of lipid and calcification within carotid plaques (P<0.001). CONCLUSIONS: Radiation caused more severe carotid artery disease than CVRF with larger CIMT and more prevalent of carotid plaque. Radiation-induced carotid plaques tended to have more intra-plaque calcifications, whereas non-radiation-induced carotid plaques had more lipids. Ultrasound aided by computer-assisted image analysis has potential for more accurate assessment of carotid atherosclerosis.

Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is the most devastating infectious disease in the 21st century with more than 2 million lives lost in less than a year. The activation of inflammasome in the host infected by SARS-CoV-2 is highly related to cytokine storm and hypercoagulopathy, which significantly contribute to the poor prognosis of COVID-19 patients. Even though many studies have shown the host defense mechanism induced by inflammasome against various viral infections, mechanistic interactions leading to downstream cellular responses and pathogenesis in COVID-19 remain unclear. The SARS-CoV-2 infection has been associated with numerous cardiovascular disorders including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The inflammatory response triggered by the activation of NLRP3 inflammasome under certain cardiovascular conditions resulted in hyperinflammation or the modulation of angiotensin-converting enzyme 2 signaling pathways. Perturbations of several target cells and tissues have been described in inflammasome activation, including pneumocytes, macrophages, endothelial cells, and dendritic cells. The interplay between inflammasome activation and hypercoagulopathy in COVID-19 patients is an emerging area to be further addressed. Targeted therapeutics to suppress inflammasome activation may have a positive effect on the reduction of hyperinflammation-induced hypercoagulopathy and cardiovascular disorders occurring as COVID-19 complications.

Vascular Tissue Engineering: Advanced Techniques and Gene Editing in Stem Cells for Graft Generation.

The common occurrence of cardiovascular diseases and the lack of proper autologous tissues prompt and promote the pressing development of tissue-engineered vascular grafts (TEVGs). Current progress on scaffold production, genetically modified cells, and use of nanotechnology-based monitoring has considerably improved the long-term patency of engineered tissue grafts. However, challenges abound in the autologous materials and manipulation of genes and cells for tissue engineering. This review overviews current development in TEVGs and discusses recent improvements in scaffolding techniques and the efficiency of gene-editing tools and their ability to fill the existing gaps in stem cell and regenerative therapies. Current advances in three-dimensional printing approaches for fabrication of engineered tissues are also reviewed together with specific biomaterials for vascular tissues. In addition, the natural and synthetic polymers that hold increasing significance for vascular tissue engineering are highlighted. Both animal models and nanotechnology-based monitoring are proposed for preclinical evaluation of engineered grafts in view of their historical significance in tissue engineering. The ultimate success of tissue regeneration, which is yet to be fully realized, depends on the optimal performance of culture systems, biomaterial constructs, and stem cells in a suitable artificial physiological environment.

Territorywide Study of Early Coronavirus Disease Outbreak, Hong Kong, China.

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10-3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

The myopia susceptibility locus vasoactive intestinal peptide receptor 2 (VIPR2) contains variants with opposite effects.

Myopia is the commonest eye disorder in the world. High myopes are predisposed to ocular pathologies. The vasoactive intestinal peptide receptor 2 (VIPR2) gene was identified as a myopia susceptibility locus by our group and another group. We continued to fine-map this locus. A case-control study was performed in 4 sequential stages with a total of 941 highly myopic subjects and 846 control subjects, all unrelated Chinese. Stage 1 experimentally genotyped 64.4% of the entire cohort for 152 single-nucleotide polymorphisms (SNPs) and Stage 2 the remaining subjects for 21 SNPs. Stage 3 combined the genotypes for 21 SNPs for the entire cohort, and identified one group of high-risk haplotypes and one group of protective haplotypes significantly associated with high myopia. Stage 4 imputed genotypes for variants in the VIPR2 region and identified two independent groups of variants: one group with high-risk minor alleles and another with protective minor alleles. Variants within each group were generally in strong linkage disequilibrium among themselves while high-risk variants were in linkage equilibrium with protective variants. Therefore, the VIPR2 locus seems to contain variants with opposite effects. This is the first study that has examined the genetic architecture of a myopia susceptibility locus in detail.

A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia.

Purpose: The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G × E) interactions in myopia susceptibility. Few such G × E interactions have been discovered to date. We aimed to test the hypothesis that genetic analysis of susceptibility to visual experience-induced myopia in an animal model would identify novel G × E interaction loci. Methods: Chicks aged 7 days (n = 987) were monocularly deprived of form vision for 4 days. A genome-wide association study (GWAS) was carried out in the 20% of chicks most susceptible and least susceptible to form deprivation (n = 380). There were 304,963 genetic markers tested for association with the degree of induced axial elongation in treated versus control eyes (A-scan ultrasonography). A GWAS candidate region was examined in the following three human cohorts: CREAM consortium (n = 44,192), UK Biobank (n = 95,505), and Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4989). Results: A locus encompassing the genes PIK3CG and PRKAR2B was genome-wide significantly associated with myopia susceptibility in chicks (lead variant rs317386235, P = 9.54e-08). In CREAM and UK Biobank GWAS datasets, PIK3CG and PRKAR2B were enriched for strongly-associated markers (meta-analysis lead variant rs117909394, P = 1.7e-07). In ALSPAC participants, rs117909394 had an age-dependent association with refractive error (-0.22 diopters [D] change over 8 years, P = 5.2e-04) and nearby variant rs17153745 showed evidence of a G × E interaction with time spent reading (effect size -0.23 D, P = 0.022). Conclusions: This work identified the PIK3CG-PRKAR2B locus as a mediator of susceptibility to visually induced myopia in chicks and suggests a role for this locus in conferring susceptibility to myopia in human cohorts.

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies.

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.

Characterization and Regulation of Gap Junctions in Porcine Ciliary Epithelium.

Purpose: Gap junctions provide a conduit between the intracellular fluids of the pigmented (PE) and non-pigmented (NPE) ciliary epithelial cells, and are therefore critical in the secretion of the aqueous humor (AH). However, opinions differ concerning the connexin (Cx) composition of the gap junctions. Therefore, we aimed to characterize the expression of Cx in the porcine ciliary epithelium (CE), a favorable model for humans; and determine the contribution of the highest expressed Cx to AH secretion. Methods: Freshly-harvested porcine CE cells were used. The mRNA and protein expressions of gap junctions were assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB), respectively. The relative gene expressions of various Cx were determined by quantitative PCR. The gap junction permeability of isolated PE-NPE cell couplets was evaluated by Lucifer Yellow dye transfer. Results: Using RT-PCR and WB, Cx43, Cx45, Cx47, Cx50, and Cx60 were present in porcine CE, with Cx43 being the most abundant isoform, having over 200-fold higher expression than other Cx. Cx43 was primarily localized in the PE-NPE interface and the basolateral membranes of PE cells. Knockdown of Cx43 by siRNA significantly reduced gene and protein expressions, resulting in reduction of transcellular fluid flow by 90%. Conclusions: Cx43 was found to be the major component of gap junctions in porcine CE. Consistent with results from a bovine model, our results support the important role of Cx43 in mediating AH secretion. This finding may shed light on the development of a novel ocular hypotensive agent.

Computer-aided assessment of regional vascularity of thyroid nodules for prediction of malignancy.

Color Doppler vascular index (VI) was assessed alone and in combination with grey-scale ultrasound (GSU) in regionally subdivided thyroid nodules in diagnosing thyroid cancer. Color Doppler sonograms of 111 thyroid nodules were evaluated by a home-developed algorithm that performed "offsetting" (algorithm for changing the area of a region of interest, ROI, without distorting the ROI's contour) and assessed peripheral, central and overall VI of thyroid nodules. Results showed that the optimum offset for dividing peripheral and central regions of nodule was 22%. At the optimum offset, the mean VI of peripheral, central, and overall regions of malignant nodules were significantly higher than those of benign nodules (26.5 ± 16.2%, 21.7 ± 19.6%, 23.8 ± 4.6% v/s 18.2 ± 16.7%, 11.9 ± 15.1% and 16.6 ± 1.8% respectively, P < 0.05). The optimum cut-off of peripheral, central, and overall VI was 19.7%, 9.1% and 20.2% respectively. When compared to GSU alone, combination of VI assessment with GSU evaluation of thyroid nodules increased the diagnostic accuracy from 58.6% to 79.3% (P < 0.05). In conclusion, a novel algorithm for regional subdivision and quantification of thyroid nodular VI in ultrasound images was established, and the optimum offset and cut-off were derived. Assessment of intranodular VI in conjunction with GSU can increase the accuracy in ultrasound diagnosis of thyroid cancer.

Genetic Association Study of KCNQ5 Polymorphisms with High Myopia.

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give Pasym values, and multiple comparisons were corrected by permutation test to give Pemp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63-0.90; Pemp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64-0.89; Pemp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.