Search

INTRODUCTION: Following acute enterovirus (EV) infection, outcomes vary based on factors like the immune response, viral cell entry receptor expression levels, tissue tropism, and genetic factors of both the host and virus. While most individuals exhibit mild, self-limited symptoms, others may suffer severe complications or prolonged infections that can lead to autoimmune disorders. METHODS: To elucidate host responses to EV infection, we performed whole exome sequencing on blood samples from both infected and uninfected individuals. Our initial focus was on genes encoding EV entry receptors-PSGL-1, SCARB2, and ANAXA2 for EV-A71, and CD155 for poliovirus-and on host genes ACBD3 and PI4KΒ, crucial for EV replication. RESULTS: Although no specific genetic variants directly associated with EV infection were identified, we discovered 118 variants across 116 genes enriched in East Asian populations through multi-layered variant filtering. These variants were further analyzed for their potential impacts on organs, biological processes, and molecular pathways. Phenome-wide association studies were conducted to refine our understanding of their contributions to EV infection susceptibility. DISCUSSION: Our findings aim to develop a predictive panel based on these 118 variants, which could help susceptible individuals during EV outbreaks, guiding targeted clinical interventions and preventative strategies.

Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS. In order to determine any precipitating causes of ASAS, we also extensively investigated established potential risk factors for ASAS in our patient and noticed that she had a marked folate deficiency requiring folic acid supplementation to prevent future episodes of ASAS as well as to repair the patients injured spinal cord. Interestingly, the patient did not display elevated levels of homocysteine nor did she possess the three pathogenic MTHFR mutations characteristic of ASAS. Although her folate deficiency did not cause responsive hyperhomocysteinemia, and she did not have pathogenic MTHFR mutations that impair the function of methylenetetrahydrofolate reductase in folate cycle, we suggest that isolated folate deficiency may play a role in adolescent cases of ASAS that, once identified, would require prompt identification and early intervention to improve the prognosis of these patients.

Background: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. Methods: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. Results: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. Conclusion: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background and Objectives: Genomic studies have identified several SNP loci associated with schizophrenia in East Asian populations. Environmental factors, particularly urbanization, play a significant role in schizophrenia development. This study aimed to identify schizophrenia susceptibility loci and characterize their biological functions and molecular pathways in Taiwanese urban Han individuals. Materials and Methods: Participants with schizophrenia were recruited from the Taiwan Precision Medicine Initiative at Tri-Service General Hospital. Genotype–phenotype association analysis was performed, with significant variants annotated and analyzed for functional relevance. Results: A total of 137 schizophrenia patients and 26,129 controls were enrolled. Ten significant variants (p < 1 × 10−5) and 15 expressed genes were identified, including rs1010840 (SOWAHC and RGPD6), rs11083963 (TRPM4), rs11619878 (LINC00355 and LINC01052), rs117010638 (AGBL1 and MIR548AP), rs1170702 (LINC01680 and LINC01720), rs12028521 (KAZN and PRDM2), rs12859097 (DMD), rs1556812 (ATP11A), rs78144262 (LINC00977), and rs9997349 (ENPEP). These variants and associated genes are involved in immune response, blood pressure regulation, muscle function, and the cytoskeleton. Conclusions: Identified variants and associated genes suggest a potential genetic predisposition to schizophrenia in the Taiwanese urban Han population, highlighting the importance of potential comorbidities, considering population-specific genetic and environmental interactions. [ABSTRACT FROM AUTHOR]

The Omicron variant of concern (VOC) has surged in many countries and replaced the previously reported VOC. To identify different Omicron strains/sublineages on a rapid, convenient, and precise platform, we report a novel multiplex real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) method in one tube based on the Omicron lineage sequence variants' information. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) subvariants were used in a PCR‐based assay for rapid identification of Omicron sublineage genotyping in 1000 clinical samples. Several characteristic mutations were analyzed using specific primers and probes for the spike gene, del69–70, and F486V. To distinguish Omicron sublineages (BA.2, BA.4, and BA.5), the NSP1:141–143del in the ORF1a region and D3N mutation in membrane protein occurring outside the spike protein region were analyzed. Results from the real‐time PCR assay for one‐tube accuracy were compared to those of whole genome sequencing. The developed PCR assay was used to analyze 400 SARS‐CoV‐2 positive samples. Ten samples determined as BA.4 were positive for NSP1:141–143del, del69–70, and F486V mutations; 160 BA.5 samples were positive for D3N, del69–70, and F486V mutations, and 230 BA.2 samples were without del69–70. Screening these samples allowed the identification of epidemic trends at different time intervals. Our novel one‐tube multiplex PCR assay was effective in identifying Omicron sublineages. [ABSTRACT FROM AUTHOR]