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 w...
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| Format: | Article |
| Language: | English |
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2023-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2023-0019 |
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| author | Baranasic Jurica Niazi Yasmeen Chattopadhyay Subhayan Rumora Lada Ćorak Lorna Dugac Andrea Vukić Jakopović Marko Samaržija Miroslav Försti Asta Knežević Jelena |
| author_facet | Baranasic Jurica Niazi Yasmeen Chattopadhyay Subhayan Rumora Lada Ćorak Lorna Dugac Andrea Vukić Jakopović Marko Samaržija Miroslav Försti Asta Knežević Jelena |
| author_sort | Baranasic Jurica |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-243c2ac89bc34003a8355a7022711126 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Sciendo |
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| series | Acta Pharmaceutica |
| spelling | doaj-art-243c2ac89bc34003a8355a70227111262025-02-03T07:04:13ZengSciendoActa Pharmaceutica1846-95582023-06-0173224325610.2478/acph-2023-0019Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer developmentBaranasic Jurica0Niazi Yasmeen1Chattopadhyay Subhayan2Rumora Lada3Ćorak Lorna4Dugac Andrea Vukić5Jakopović Marko6Samaržija Miroslav7Försti Asta8Knežević Jelena91Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia2Hopp Children’s Cancer Center (KiTZ)Heidelberg, Germany3Division of Pediatric Neurooncology German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK)Heidelberg, Germany5Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of ZagrebZagreb, Croatia6Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia6Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia6Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia6Clinical Department for Respiratory Diseases Jordanovac, University Hospital Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia2Hopp Children’s Cancer Center (KiTZ)Heidelberg, Germany1Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, CroatiaChronic 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.https://doi.org/10.2478/acph-2023-0019gwassnpcopdlung cancerimmune-related genesnf-κb |
| spellingShingle | Baranasic Jurica Niazi Yasmeen Chattopadhyay Subhayan Rumora Lada Ćorak Lorna Dugac Andrea Vukić Jakopović Marko Samaržija Miroslav Försti Asta Knežević Jelena Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development Acta Pharmaceutica gwas snp copd lung cancer immune-related genes nf-κb |
| title | Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development |
| title_full | Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development |
| title_fullStr | Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development |
| title_full_unstemmed | Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development |
| title_short | Germline variants of the genes involved in NF-kB activation are associated with the risk of COPD and lung cancer development |
| title_sort | germline variants of the genes involved in nf kb activation are associated with the risk of copd and lung cancer development |
| topic | gwas snp copd lung cancer immune-related genes nf-κb |
| url | https://doi.org/10.2478/acph-2023-0019 |
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