| Summary: | 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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