Safarinejad Mohammad Reza, Shafiei Nayyer, Safarinejad Shiva
Growth Horm IGF Res. 2011 Jun;21(3):146-54. doi: 10.1016/j.ghir.2011.03.008. Epub 2011 May 4.
The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH.
胰岛素样生长因子-I（IGF-I）的生物利用度受结合蛋白胰岛素样生长因子结合蛋白-3（IGFBP-3）的控制。此外，IGFBP-3是一种强大的抗增殖蛋白，可引发前列腺癌细胞凋亡并抑制其增殖。我们开展这项研究以调查IGFBP-3基因多态性与IGF-I和IGFBP-3血清水平之间的关联，以及前列腺癌（PCa）和良性前列腺增生（BPH）的发病率。从所有参与者采集的外周血样本中进行DNA提取。使用属于该基因区域的合适引物，通过聚合酶链反应-限制性片段长度多态性（PCR-RLFP）技术扩增所需区域。我们还测量了血清IGF-I和IGFBP-3水平。IGFBP-3 -202 A/C多态性基因型频率在PCa患者与对照组之间（χ(2)=6.27，自由度=2.0，P=0.026）以及BPH患者与对照组之间（χ(2)=11.57，自由度=4.0，P=0.014）显示出显著差异。与对照组相比，PCa和BPH患者中AA基因型频率显著降低，且该基因型发生PCa和BPH的风险相应降低（PCa；比值比=0.28，95%置信区间=0.17 - 0.44，P=0.0001；BPH：比值比=0.48，95%置信区间=0.29 - 0.77，P=0.001）。年龄调整后的血清IGFBP-3平均浓度在AA基因型个体中最高，在存在1个或2个C等位基因拷贝时呈逐步显著降低（分别为4577 ng/ml、3929 ng/ml和3349 ng/ml）。与对照组相比，PCa和BPH患者的血清IGF-1水平（分别为P=0.001和P=0.01）以及IGFBP-3水平（分别为P=0.001和P=0.01）较低。IGFBP-3基因多态性中的AA基因型与PCa和BPH风险降低相关。IGF-I和IGFBP-3浓度均与PCa和BPH的风险改变相关。
