Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention |
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| Authors: | Konstantina Vogiatzi Vassilis Voudris Stavros Apostolakis Georgios E. Kochiadakis Sofia Thomopoulou Apostolos Zaravinos Demetrios A. Spandidos |
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| Affiliation: | 1. Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Creece;2. Department of Cardiology, Onassis Cardiac Surgery Centre, Athens, Greece;3. Department of Cardiology, University Hospital of Crete, Heraklion, Crete, Greece;1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan;2. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan;3. First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan;4. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan;5. Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan;6. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;7. Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka, Japan;8. Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan;9. Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan;10. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan;11. Department of Gastroenterology, Sapporo Kosei Hospital, Sapporo, Japan;12. Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan;13. Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, Aizu-wakamatsu, Japan;14. Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan;1. Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan;2. Division of Pathology, Prefectural University of Hiroshima of Human Life and Environmental Science, Hiroshima, Japan;3. Advanced Medical Skill Training Center, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan;1. MD, Anesthesia Study Center, Goiânia, GO, Brazil;2. TSA (Superior Title in Anesthesiology)/SBA (Brazilian Society of Anesthesiology); PhD in Medicine, Santa Casa de São Paulo, Head of Department of Surgery, Universidade Federal de Goiás; Director of Professional Defense, SBA; Specialist in Intensive Care Medicine, Goiânia, GO, Brazil;3. Clinical Pathologist, Hospital Anis Rassi de Goiânia; Director, Hospital Anis Rassi de Goiânia, GO, Brazil;4. Professor of Pathological Anatomy, Universidade Federal de Goiás, Goiânia, GO, Brazil;5. MD, Anesthesiology Department, Hospital das Clinicas, UFG, Anesthesia Study Center, Goiania, GO, Brazil Received from Anesthesia Study Center, Goiania, GO, Brazil;1. Department of Surgery, Koshigaya Municipal Hospital, Higashikoshigaya 10-47-1, Koshigayashi, Saitama 343-8577, Japan;2. Department of Pathology, Koshigaya Municipal Hospital, Higashikoshigaya 10-47-1, Koshigayashi, Saitama 343-8577, Japan |
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| Abstract: | Regulated on activation, normal T cell expressed and secreted (RANTES) gene promoter is a regulatory region and a site of notable genetic diversity. In order to explore a possible interaction between RANTES promoter genetic diversity and susceptibility to coronary artery disease (CAD) and in stent restenosis (ISR), we initially sequenced a locus extending from - 516 to 40 covering the entire region of the RANTES promoter in 100 subjects randomly selected from our cohort. Four single nucleotide polymorphisms (SNPs) were identified: - 403G/A, - 256G/A, - 109C/T and - 28C/G. The frequency of the - 109C/T and - 256G/A variations was < 0.01, and was considered to be of limited significance. The frequency of the - 403G/A and - 28C/G polymorphisms was evaluated in the entire sample, which consisted of 118 patients subjected to percutaneous coronary intervention (PCI) without ISR on angiographic re-evaluation (no IRS group), 74 CAD patients with ISR on angiographic re-evaluation (IRS group) and 146 controls without angiographic evidence of CAD (no CAD group). No association was established between the RANTES promoter genotype and ISR. A genotype-phenotype interaction was observed between the - 403G/A polymorphism and CAD. The - 403A homozygotes were significantly more common in the CAD group than in the controls. The severity of CAD among case subjects, expressed as the mean number of diseased vessels, was significantly higher among - 403A homozygotes as compared to wild-type homozygotes and heterozygotes. In conclusion, the RANTES - 403A allele was associated with the presence and severity of CAD independently of conventional cardiovascular risk factors. The RANTES promoter genotype did not influence susceptibility to ISR in patients subjected to PCI. |
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