Division of Genomic Epidemiology and Clinical Trials, Dept of Advanced Medical Science, Nihon University School of Medicine, 30-1 Itabashi-ku, Tokyo, Japan.
Hereditas. 2010 Oct;147(5):215-24. doi: 10.1111/j.1601-5223.2010.02174.x. Epub 2010 Oct 13.
During adult life, the insulin/insulin-like growth factor1 (IGF1) signaling pathway plays an important role in cardiovascular function. Several reports have suggested that low baseline levels of IGF1 increase the risk of fatal ischemic heart disease. Thus, IGF1 may be involved in cardiovascular disease. The aim of the present study was to investigate the relationship between the human IGF1 gene and myocardial infarction (MI) in the Japanese population via the use of single nucleotide polymorphisms (SNPs). After selecting six SNPs in the human IGF1 gene (rs2162679, rs7956547, rs2288378, rs2072592, rs978458 and rs6218), we performed a case-control study using each of the SNPs and haplotypes in 320 MI patients and 307 non-MI controls. Multiple logistic regression analysis demonstrated that the GG+GA variant of rs2162679 (p=0.009) and the AA+GA variant of rs2072592 (p=0.026) exhibited a resistant effect for MI. The haplotype-based case-control study revealed that the frequency of the A-T-G-G haplotype for rs2162679-rs7956547-rs2072592-rs978458 was significantly higher in the MI group (47.3%) as compared to the non-MI group (41.4%) (p=0.037, odds ratio=1.270). The frequency of the A-T-G-T haplotype for rs2162679-rs7956547-rs978458-rs6218 was also significantly higher in the MI group (47.3%) as compared to the non-MI group (41.3%) (p=0.033, odds ratio=1.276). The current results suggest that specific SNPs and haplotypes can be utilized as genetic markers for MI risk or MI resistance. In addition, IGF1 or a neighboring gene might be associated with increased or decreased susceptibility to MI.
在成年期，胰岛素/胰岛素样生长因子 1（IGF1）信号通路在心血管功能中起着重要作用。有几项报告表明，IGF1 的基线水平较低会增加致命性缺血性心脏病的风险。因此，IGF1 可能与心血管疾病有关。本研究旨在通过使用单核苷酸多态性（SNP）来研究人类 IGF1 基因与日本人心肌梗死（MI）之间的关系。在选择人类 IGF1 基因中的 6 个 SNP（rs2162679、rs7956547、rs2288378、rs2072592、rs978458 和 rs6218）后，我们使用每个 SNP 和单体型对 320 例 MI 患者和 307 例非 MI 对照进行了病例对照研究。多变量逻辑回归分析表明，rs2162679 的 GG+GA 变异（p=0.009）和 rs2072592 的 AA+GA 变异（p=0.026）对 MI 具有抗性作用。基于单体型的病例对照研究表明，rs2162679-rs7956547-rs2072592-rs978458 单体型的 A-T-G-G 频率在 MI 组（47.3%）明显高于非 MI 组（41.4%）（p=0.037，比值比=1.270）。rs2162679-rs7956547-rs978458-rs6218 单体型的 A-T-G-T 频率在 MI 组（47.3%）也明显高于非 MI 组（41.3%）（p=0.033，比值比=1.276）。目前的结果表明，特定的 SNP 和单体型可用作 MI 风险或 MI 抗性的遗传标志物。此外，IGF1 或邻近基因可能与 MI 易感性的增加或减少有关。
