| 1. |
- Alehagen, Urban, et al.
(author)
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PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men
- 2016
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In: BMC Medical Genetics. - : BIOMED CENTRAL LTD. - 1471-2350. ; 17:62
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Journal article (peer-reviewed)abstract
- Background: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. Methods: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. Results: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. Conclusion: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.
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| 2. |
- Dimberg, Jan, et al.
(author)
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Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients
- 2016
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY-BLACKWELL. - 0903-4641 .- 1600-0463. ; 124:9, s. 736-740
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Journal article (peer-reviewed)abstract
- The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G amp;gt; A) and XRCC6 (rs2267437, C amp;gt; G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients. However, we showed that the carriers of allele A in XRCC1 (rs25487, G amp;gt; A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12-2.41, p = 0.012).
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| 3. |
- Gacic, Jelena, et al.
(author)
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Imatinib reduces cholesterol uptake and matrix metalloproteinase activity in human THP-1 macrophages
- 2016
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In: Pharmacological Reports. - : POLISH ACAD SCIENCES INST PHARMACOLOGY. - 1734-1140 .- 2299-5684. ; 68:1, s. 1-6
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Journal article (peer-reviewed)abstract
- Background: Imatinib mesylate (Glivec, formerly STI-571) is a selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. However, there are reports suggesting that imatinib could be atheroprotective by lowering plasma low-density lipoprotein (LDL). Aim: To investigate the potential inhibitory effect of imatinib on cholesterol uptake in human macrophages as well as its effect on matrix metalloproteinase (MMP) activity. Methods and results: Uptake of fluorescence-labeled LDL was analyzed using flow cytometry. Macrophages treated with imatinib showed a 23.5%, 27%, and 15% decrease in uptake of native LDL (p < 0.05), acetylated LDL (p < 0.01), and copper-modified oxidized LDL (p < 0.01), respectively. Gel based zymography showed that secretion and activity of MMP-2 and MMP-9 were inhibited by imatinib. Using GeneChip Whole Transcript Expression array analysis, no obvious gene candidates involved in the mechanisms of cholesterol metabolism or MMP regulation were found to be affected by imatinib. Instead, we found that imatinib up-regulated microRNA 155 (miR155) by 43.8% and down-regulated ADAM metallopeptidase domain 28 (ADAM28) by 41.4%. Both genes could potentially play an atheroprotective role and would be interesting targets in future studies. Conclusion: Our results indicate that imatinib causes post-translational inhibition with respect to cholesterol uptake and regulation of MMP-2 and MMP-9. More research is needed to further evaluate the role of imatinib in the regulation of other genes and processes. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
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| 4. |
- Slind Olsen, Renate, et al.
(author)
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Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer.
- 2016
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In: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 55:4, s. 474-479
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Journal article (peer-reviewed)abstract
- BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC).MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression.RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005).CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients.
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