MicroRNAs (MiRNAs) belong to a class of small non‐coding regulatory RNAs that act through repression of protein expression at post‐transcriptional level and emerge to play important roles in many physiological and pathophysiological processes. MiR‐146a is a miRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. In this review, we focus on the recent progress in functional role of miR‐146a in innate immune, inflammatory response, virus infection and human diseases. Together, these findings indicate that manipulation of miR‐146a expression may represent a potential new therapy for several human diseases. Potential use of miR‐146a as a biomarker for disease diagnosis, prevention and treatment is also discussed.
Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R: 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.
In this study, the 5' promoter region of MHC class I chain-related gene B (MICB) was investigated in 104 healthy, unrelated Han individuals recruited from northern China, using polymerase chain reaction (PCR)-sequencing methodology. Fifteen variable sites were detected, which showed a mosaic pattern of significant global linkage disequilibrium (LD). Eleven different 5' promoter haplotypes were identified. MICB 5' promoter haplotype-9 carrying CT deletion at positions -139/-138, which is associated with decreased MICB promoter activity, was present in 26.9% of MICB alleles and was linked to MICB*002:01, MICB*008, and MICB*014 in this population. In addition, rs3828913 (position -176) and rs3828914 (position -152) were located adjacent to HSRE and GC box in MICB promoter, respectively. Sixteen extended haplotypes (EH) incorporating the MICB 5' promoter and MICB coding region were observed in this population, eight of which were in significant LD. Phylogenetic analysis of 5' promoter refined MICB sub-lineage structure indicated that MICB*005:02, the most common MICB allele, consists of five sub-lineages. Ewens-Watterson homozygosity statistics at MICB 5' promoter region were consistent with neutral expectations. Our study has shed new insight into MICB genetic variation at population level, suggesting that binding sites for transcription factors in MICB promoter could be interrupted by polymorphisms within this region, resulting in allele-specific regulation. The data will facilitate the understanding of regulation of MICB gene transcription, and will inform studies of evolution of the major histocompatibility complex (MHC) gene complex.
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