In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease
博士 === 中山醫學大學 === 生化暨生物科技研究所 === 101 === Coronary artery disease (CAD) was the second leading cause of death for the past three years in Taiwan. The major cause of CAD is coronary artery atherosclerosis, a chronic inflammatory disease. Prior research has demonstrated the association between cytokine...
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ndltd-TW-101CSMU51070032015-10-13T22:57:21Z http://ndltd.ncl.edu.tw/handle/02188608142239905825 In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease 台灣族群中單核細胞趨化蛋白-1及類胰島素生長因-1的基因多型性與冠狀動脈疾病的相關性 Hsiu-Ling Lin 林秀玲 博士 中山醫學大學 生化暨生物科技研究所 101 Coronary artery disease (CAD) was the second leading cause of death for the past three years in Taiwan. The major cause of CAD is coronary artery atherosclerosis, a chronic inflammatory disease. Prior research has demonstrated the association between cytokines and their receptors, such as monocyte chemoattractant protein-1 (MCP-1), Interleukin -6 (IL-6), and Interleukin -1 beta (IL-1 beta), Insulin-like growth factor-I (IGF-I), and Insulin-like growth factor binding protein III(IGFBP-3) which accumulate within the vessel walls of the coronary arteries during the initial phase of atherosclerosis. Previous studies suggested that increased serum MCP-1 levels associated with risk of CAD or other atherosclerotic vascular diseases. In addition, elevated circulating IGF-I and IGFBP-3 levels may contribute to increased CAD risk, Moreover, recent studies have demonstrated that polymorphisms in a gene influences its protein expression which in turn change the susceptibility to many diseases. Therefore, this study investigated the relationships among MCP-1, CCR-2, IGF-1 and IGFBP-3 genetic polymorphisms and CAD in the Taiwanese population. There 392 non-CAD controls and 216 patients with CAD, were recruited in this study and subjected to polymerase chain reaction -restriction fragment length polymorphism (PCR–RFLP) and real- time polymerase chain to evaluate the effects of MCP-12518G/A, CCR2-V64I, IGF-1+1770, IGF-1+6930 and IGFBP-3 -200 polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR =1.629; 95 % CI = 1.003–2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006–2.270), had a higher risk of CAD as compared with AA genotypes. And least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD (OR = 1.486; 95 % CI = 1.026–2.154). G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p<0.05), it was also shown that a significant association with the IGF-I +1770 gene polymorphism and increased risk of CAD. Furthermore, CAD patients between with a minimum of one mutant C allele in IGF-I +1770 and one mutant A allele in IGF + 6093 gene polymorphism had significantly high blood pressure including systolic blood pressure (SBP; P = 0.025; 0.023) and diastolic blood pressure (DBP; P = 0.004; 0.006). What is more, CAD patients with IGF-I +6093 G/A gene polymorphism had a 1.695-fold elevated risk of congestive heart failure (CHF), compared to CAD patients with the G/G homozygote. Another of the IGFBP-3 −202 genetic polymorphism for the CAD group with a minimum of one mutant C allele, A/C or C/C, had a 0.459-fold (95%, CI = 0.222 to 0.947) significantly decreased risk of stroke, compared to A/A homozygote patients. In conclusion, MCP-1-2518G and CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518 G allele could be through effects on AF in CAD patients. Polymorphism of IGF-I +1770 was associated with increased CAD risk. In CAD patients, the contributions of IGF-I +1770 and +6093 could be through the effect on blood pressure in CAD patients. The polymorphism of IGFBP-3 −202 may have an association with decreased stroke risk in CAD patients. With further investigation, confirm the role of MCP-1/CCR-2 and the regulatory mechanism of IGFI and IGFBP-3 in CAD might be potential candidates for the new therapy and practicable diagnosis of CAD. 謝易修 翁國昌 2013 學位論文 ; thesis 81 zh-TW |
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博士 === 中山醫學大學 === 生化暨生物科技研究所 === 101 === Coronary artery disease (CAD) was the second leading cause of death for the past three years in Taiwan. The major cause of CAD is coronary artery atherosclerosis, a chronic inflammatory disease. Prior research has demonstrated the association between cytokines and their receptors, such as monocyte chemoattractant protein-1 (MCP-1), Interleukin -6 (IL-6), and Interleukin -1 beta (IL-1 beta), Insulin-like growth factor-I (IGF-I), and Insulin-like growth factor binding protein III(IGFBP-3) which accumulate within the vessel walls of the coronary arteries during the initial phase of atherosclerosis. Previous studies suggested that increased serum MCP-1 levels associated with risk of CAD or other atherosclerotic vascular diseases. In addition, elevated circulating IGF-I and IGFBP-3 levels may contribute to increased CAD risk, Moreover, recent studies have demonstrated that polymorphisms in a gene influences its protein expression which in turn change the susceptibility to many diseases. Therefore, this study investigated the relationships among MCP-1, CCR-2, IGF-1 and IGFBP-3 genetic polymorphisms and CAD in the Taiwanese population. There 392 non-CAD controls and 216 patients with CAD, were recruited in this study and subjected to polymerase chain reaction -restriction fragment length polymorphism (PCR–RFLP) and real- time polymerase chain to evaluate the effects of MCP-12518G/A, CCR2-V64I, IGF-1+1770, IGF-1+6930 and IGFBP-3 -200 polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR =1.629; 95 % CI = 1.003–2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006–2.270), had a higher risk of CAD as compared with AA genotypes. And least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD (OR = 1.486; 95 % CI = 1.026–2.154). G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p<0.05), it was also shown that a significant association with the IGF-I +1770 gene polymorphism and increased risk of CAD. Furthermore, CAD patients between with a minimum of one mutant C allele in IGF-I +1770 and one mutant A allele in IGF + 6093 gene polymorphism had significantly high blood pressure including systolic blood pressure (SBP; P = 0.025; 0.023) and diastolic blood pressure (DBP; P = 0.004; 0.006). What is more, CAD patients with IGF-I +6093 G/A gene polymorphism had a 1.695-fold elevated risk of congestive heart failure (CHF), compared to CAD patients with the G/G homozygote. Another of the IGFBP-3 −202 genetic polymorphism for the CAD group with a minimum of one mutant C allele, A/C or C/C, had a 0.459-fold (95%, CI = 0.222 to 0.947) significantly decreased risk of stroke, compared to A/A homozygote patients. In conclusion, MCP-1-2518G and CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518 G allele could be through effects on AF in CAD patients. Polymorphism of IGF-I +1770 was associated with increased CAD risk. In CAD patients, the contributions of IGF-I +1770 and +6093 could be through the effect on blood pressure in CAD patients. The polymorphism of IGFBP-3 −202 may have an association with decreased stroke risk in CAD patients. With further investigation, confirm the role of MCP-1/CCR-2 and the regulatory mechanism of IGFI and IGFBP-3 in CAD might be potential candidates for the new therapy and practicable diagnosis of CAD.
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author2 |
謝易修 |
author_facet |
謝易修 Hsiu-Ling Lin 林秀玲 |
author |
Hsiu-Ling Lin 林秀玲 |
spellingShingle |
Hsiu-Ling Lin 林秀玲 In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
author_sort |
Hsiu-Ling Lin |
title |
In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
title_short |
In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
title_full |
In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
title_fullStr |
In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
title_full_unstemmed |
In Taiwan the polymorphisms of MCP-1/ CCR-2 and IGF-1/IGFBP-3 associated with coronary artery disease |
title_sort |
in taiwan the polymorphisms of mcp-1/ ccr-2 and igf-1/igfbp-3 associated with coronary artery disease |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/02188608142239905825 |
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