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Yilmaz B, Genc GC, Celik SK, Cinar BP, Acikgoz M, Dursun A. PARP-1 gene promoter region may be associated with progression in multiple sclerosis. Clin Chim Acta 2025; 572:120275. [PMID: 40169083 DOI: 10.1016/j.cca.2025.120275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 03/28/2025] [Accepted: 03/28/2025] [Indexed: 04/03/2025]
Abstract
Multiple Sclerosis (MS) is a leading cause of disability among young adults. Most cases begin with relapsing-remitting MS (RRMS) and can transition to secondary progressive MS (SPMS) over time. It is known that the inflammatory status of the central nervous system changes during the progression of MS. Poly (ADP-ribose) polymerase-1 (PARP-1) is an enzyme involved in several cellular processes. Our study aimed to investigate the relationship between MS and the PARP-1 gene. We analyzed the PARP-1 gene's missense polymorphism rs1136410, promoter region polymorphism rs7527192, and 3'UTR polymorphism rs8679 in 123 MS patients and 168 healthy controls using the PCR-RFLP method. We examined genotype and allele frequency distributions among case-control groups and clinical subgroups. We observed that the CC genotype of rs7527192 polymorphism was increased in SPMS patients compared to controls. We also found that the CC genotype and C allele frequency were increased in the EDSS score > 3-6 group compared to healthy controls. The C allele frequency was increased in EDSS score > 3-6 compared to those with ≤ 3 and ≥ 6. When the results observed in our study are evaluated with the known effect of PARP-1 on the inflammasome pathway, we suggest that rs7527192 may be effective in the progression process through the activity of the PARP-1 inflammasome pathway.
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Affiliation(s)
- Busra Yilmaz
- Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
| | - Gunes Cakmak Genc
- Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Sevim Karakas Celik
- Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Bilge Piri Cinar
- Department of Neurology, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Mustafa Acikgoz
- Department of Neurology, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Ahmet Dursun
- Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
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Vital N, Antunes S, Louro H, Vaz F, Simões T, Penque D, Silva MJ. Environmental Tobacco Smoke in Occupational Settings: Effect and Susceptibility Biomarkers in Workers From Lisbon Restaurants and Bars. Front Public Health 2021; 9:674142. [PMID: 34150711 PMCID: PMC8213454 DOI: 10.3389/fpubh.2021.674142] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/10/2021] [Indexed: 11/23/2022] Open
Abstract
Environmental tobacco smoke (ETS) has been recognized as a major health hazard by environmental and public health authorities worldwide. In Portugal, smoke-free laws are in force for some years, banning smoking in most indoor public spaces. However, in hospitality venues such as restaurants and bars, owners can still choose between a total smoke-free policy or a partial smoking restriction with designated smoking areas, if adequate reinforced ventilation systems are implemented. Despite that, a previous study showed that workers remained continuously exposed to higher ETS pollution in Lisbon restaurants and bars where smoking was still allowed, comparatively to total smoke-free venues. This was assessed by measurements of indoor PM2.5 and urinary cotinine, a biomarkers of tobacco smoke exposure, demonstrating that partial smoking restrictions do not effectively protect workers from ETS. The aim of the present work was to characterize effect and susceptibility biomarkers in non-smokers from those hospitality venues occupationally exposed to ETS comparatively to non-exposed ones. A group of smokers was also included for comparison. The sister chromatid exchange (SCE), micronucleus (MN) and comet assays in whole peripheral blood lymphocytes (PBLs) and the micronucleus assay in exfoliated buccal cells, were used as biomarkers of genotoxicity. Furthermore, a comet assay after ex vivo challenge of leukocytes with an alkylating agent, ethyl methanesulfonate (EMS), was used to analyze the repair capacity of those cells. Genetic polymorphisms in genes associated with metabolism and DNA repair were also included. The results showed no clear association between occupational exposure to ETS and the induction of genotoxicity. Interestingly, the leukocytes from non-smoking ETS-exposed individuals displayed lower DNA damage levels in response to the ex vivo EMS challenge, in comparison to those from non-exposed workers, suggesting a possible adaptive response. The contribution of individual susceptibility to the effect biomarkers studied was unclear, deserving further investigation.
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Affiliation(s)
- Nádia Vital
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
| | - Susana Antunes
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
| | - Henriqueta Louro
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Fátima Vaz
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Tânia Simões
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
| | - Deborah Penque
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Maria João Silva
- Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
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