Jurica Baranasic, Yasmeen Niazi, Subhayan Chattopadhyay, Lada Rumora, Lorna Ćorak, Andrea Vukić Dugac, Marko Jakopović, Miroslav Samaržija, Asta Försti, Jelena Knežević
{"title":"参与NF-kB激活的基因的种系变异与COPD和肺癌发展的风险相关。","authors":"Jurica Baranasic, Yasmeen Niazi, Subhayan Chattopadhyay, Lada Rumora, Lorna Ćorak, Andrea Vukić Dugac, Marko Jakopović, Miroslav Samaržija, Asta Försti, Jelena Knežević","doi":"10.2478/acph-2023-0019","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a <i>p</i>-value < 3.3 × 10<sup>-5</sup> were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (<i>BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1</i>) to be associated with the COPD risk and two with the LC risk (<i>HLA-C, HLA-B</i>), with statistical significance. We also identified two SNPs located in the <i>IL2RA</i> gene associated with LC (rs2386841; <i>p</i> = 1.86 × 10<sup>-4</sup>) and COPD (rs11256442; <i>p</i> = 9.79 × 10<sup>-3</sup>) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 2","pages":"243-256"},"PeriodicalIF":2.1000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development.\",\"authors\":\"Jurica Baranasic, Yasmeen Niazi, Subhayan Chattopadhyay, Lada Rumora, Lorna Ćorak, Andrea Vukić Dugac, Marko Jakopović, Miroslav Samaržija, Asta Försti, Jelena Knežević\",\"doi\":\"10.2478/acph-2023-0019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a <i>p</i>-value < 3.3 × 10<sup>-5</sup> were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (<i>BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1</i>) to be associated with the COPD risk and two with the LC risk (<i>HLA-C, HLA-B</i>), with statistical significance. We also identified two SNPs located in the <i>IL2RA</i> gene associated with LC (rs2386841; <i>p</i> = 1.86 × 10<sup>-4</sup>) and COPD (rs11256442; <i>p</i> = 9.79 × 10<sup>-3</sup>) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.</p>\",\"PeriodicalId\":7034,\"journal\":{\"name\":\"Acta Pharmaceutica\",\"volume\":\"73 2\",\"pages\":\"243-256\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Pharmaceutica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2478/acph-2023-0019\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Pharmaceutica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2478/acph-2023-0019","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development.
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10-5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10-4) and COPD (rs11256442; p = 9.79 × 10-3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.
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AP is an international, multidisciplinary journal devoted to pharmaceutical and allied sciences and contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell biology, cell cultures, clinical pharmacy, drug design, drug delivery, drug disposition, drug stability, gene technology, medicine (including diagnostics and therapy), medicinal chemistry, metabolism, molecular modeling, pharmacology (clinical and animal), peptide and protein chemistry, pharmacognosy, pharmacoepidemiology, pharmacoeconomics, pharmacodynamics and pharmacokinetics, protein design, radiopharmaceuticals, and toxicology.
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