Dataset Information

TLR10 and NFKBIA contributed to the risk of hip osteoarthritis: systematic evaluation based on Han Chinese population.

ABSTRACT: Multiple lines of evidence have confirmed the importance of genetic factors for hip osteoarthritis (HOA). Our study aimed to investigate the associations of TLR10 and NFKBIA with respect to the HOA risk in Han Chinese individuals. A total of 1,043 HOA patients and 2,664 controls were recruited. Then, 23 tag single-nucleotide polymorphisms (SNPs) in the TLR10 and NFKBIA genes were selected for genotyping. Genetic association analyses were conducted in both single-marker and haplotype-based ways. Gene by gene, two-way interactions were analysed using a case-only method. Multiple bioinformatics tools were utilised to examine the potential functional significance of the SNPs. Two significant SNPs, rs11096957 (OR?=?1.26, P?=?1.35?×?10-5) and rs2273650 (OR?=?1.2, P?=?1.57?×?10-3), were significantly associated with HOA risk. Rs11096957 was also associated with the severity of the HOA. Bioinformatics analysis indicated that the allele T of rs2273650 would create new miRNA/SNP target duplexes, which suggests that rs2273650 could alter the NFKBIA expression by affecting the miRNA/SNP target duplexes. Our study identified significant association signals from NFKBIA with HOA for the first time, and it also confirmed the contribution of TLR10 to the HOA risk. These findings would provide clues for identifying individuals at high risk of HOA.

SUBMITTER: Tang H

PROVIDER: S-EPMC6035240 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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TLR10 and NFKBIA contributed to the risk of hip osteoarthritis: systematic evaluation based on Han Chinese population.

Tang Hongtao H Cheng Zhenzhen Z Ma Wenlong W Liu Youwen Y Tong Zhaofang Z Sun Ruibo R Liu Hongliang H

Scientific reports 20180706 1

Multiple lines of evidence have confirmed the importance of genetic factors for hip osteoarthritis (HOA). Our study aimed to investigate the associations of TLR10 and NFKBIA with respect to the HOA risk in Han Chinese individuals. A total of 1,043 HOA patients and 2,664 controls were recruited. Then, 23 tag single-nucleotide polymorphisms (SNPs) in the TLR10 and NFKBIA genes were selected for genotyping. Genetic association analyses were conducted in both single-marker and haplotype-based ways. ...[more]

PMID: 29980729

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Project description:Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes.

Dataset Information

TLR10 and NFKBIA contributed to the risk of hip osteoarthritis: systematic evaluation based on Han Chinese population.

Publications

TLR10 and NFKBIA contributed to the risk of hip osteoarthritis: systematic evaluation based on Han Chinese population.

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