Joanna Mikołajczyk-Stecyna1, Aleksandra Korcz2, Marcin Gabriel3, Katarzyna Pawlaczyk4, Grzegorz Oszkinis3, Ryszard Słomski5. 1. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address: joannastecyna@wp.pl. 2. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. 3. Department of General and Vascular Surgery, Poznan University of Medical Sciences, Poznan, Poland. 4. Department of Hypertension, Angiology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland. 5. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland.
Abstract
OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) is connected with abnormal extracellular matrix remodeling, with the assistance of extracellular matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A decrease in tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression was detected in AAA patients. Recently, a -418 G/C (rs8179090) polymorphism of the TIMP2 gene promoter, influencing the transcription rate of the gene, has been described. This study investigated whether the -418 G/C gene polymorphism is associated with AAA in the Polish population. METHODS: The TIMP2 gene promoter polymorphism was evaluated by polymerase chain reaction, followed by restriction enzyme analysis and pyrosequencing in 128 patients affected by AAA and in 180 individuals included as references. The control group was directly matched to patients according to known risk factors for vascular diseases. RESULTS: The frequency of the C allele was significantly higher in AAA patients than in the control group (odds ratio [OR], 2.516; P = .0005). The distribution of genotypes also differed significantly between the groups (CC + CG vs GG: OR, 2.906; P = .0037) or was close to being significantly different (CC vs GG + GC: OR, 2.144; P = .0501). A similar trend was observed in men but not in women. The multivariate logistic regression analysis indicated the TIMP2 gene promoter polymorphism is risk factor of AAA in the Polish population, with an adjusted OR of 4.99, when applied to a dominant inheritance model. CONCLUSIONS: Our study supports the hypothesis that TIMP2 and the -418G/C polymorphism located in the promoter of the TIMP2 gene are important in AAA pathophysiology.
OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) is connected with abnormal extracellular matrix remodeling, with the assistance of extracellular matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A decrease in tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression was detected in AAA patients. Recently, a -418 G/C (rs8179090) polymorphism of the TIMP2 gene promoter, influencing the transcription rate of the gene, has been described. This study investigated whether the -418 G/C gene polymorphism is associated with AAA in the Polish population. METHODS: The TIMP2 gene promoter polymorphism was evaluated by polymerase chain reaction, followed by restriction enzyme analysis and pyrosequencing in 128 patients affected by AAA and in 180 individuals included as references. The control group was directly matched to patients according to known risk factors for vascular diseases. RESULTS: The frequency of the C allele was significantly higher in AAA patients than in the control group (odds ratio [OR], 2.516; P = .0005). The distribution of genotypes also differed significantly between the groups (CC + CG vs GG: OR, 2.906; P = .0037) or was close to being significantly different (CC vs GG + GC: OR, 2.144; P = .0501). A similar trend was observed in men but not in women. The multivariate logistic regression analysis indicated the TIMP2 gene promoter polymorphism is risk factor of AAA in the Polish population, with an adjusted OR of 4.99, when applied to a dominant inheritance model. CONCLUSIONS: Our study supports the hypothesis that TIMP2 and the -418G/C polymorphism located in the promoter of the TIMP2 gene are important in AAA pathophysiology.
Authors: Luis García-Onrubia; Fco Javier Valentín-Bravo; Rosa M Coco-Martin; Rogelio González-Sarmiento; J Carlos Pastor; Ricardo Usategui-Martín; Salvador Pastor-Idoate Journal: Int J Mol Sci Date: 2020-08-18 Impact factor: 5.923
Authors: J Mazuchová; E Halašová; J Mazuch; M Šarlinová; V Valentová; M Franeková; Š Zelník; K Krkošková; K Javorka; M Péč; M Grendár Journal: Physiol Res Date: 2020-12-31 Impact factor: 1.881