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Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.

ABSTRACT: PURPOSE: Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH). METHODS: Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH). RESULTS: We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 - rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10(-3); OR 0.39, 95 % confidence intervals (CI) 0.22-0.7) and increased risk (P = 2.0 x 10(-5)-6.0 x 10(-4); OR 3.17-3.73) effects for ONFH, respectively. CONCLUSIONS: These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients.

SUBMITTER: Kim HS

PROVIDER: S-EPMC3824903 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.

Kim Hak Soo HS Bae Sang-Cheol SC Kim Tae-Ho TH Kim Shin-Yoon SY

International orthopaedics 20130618 11

<h4>Purpose</h4>Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms ...[more]

PMID: 23775455

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Project description:BackgroundSystemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy.MethodsCurcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review.Results201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified.ConclusionThe present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

Dataset Information

Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.

Publications

Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.

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