Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
Neurosci Lett. 2011 Sep 1;501(3):128-31. doi: 10.1016/j.neulet.2011.07.001. Epub 2011 Jul 12.
Growing evidence suggests that iron accumulation in the substantia nigra (SN) is involved in the pathology of Parkinson's diseases (PD). Divalent metal transporter 1 (DMT1) is an endogenous transporter for ferrous iron, the levels of which are significantly increased in the SN in postmortem PD brains. To study the possible association of DMT1 gene with PD occurrence, one mutation (1303C/A) and two single nucleotide polymorphisms (SNPs) (1254T/C and IVS4+44C/A) in DMT1 gene were investigated in 192 PD patients in a Han Chinese population and 193 healthy controls by method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Direct sequencing was performed in 10% of the samples to validate the genotyping results. Our results failed to find any significant association between the tested genotypes, alleles or mutation and PD, however, a haplotype (C alleles of 1254T and IVS4+44C/A polymorphisms) occurred at greater frequencies in PD subjects compared with that of control (18.2% versus 11.4%, OR=1.72, 95% CI=1.15-2.59, P=0.01). These results suggest that CC haplotype in DMT1 gene is a possible risk factor for PD in this Han Chinese population.
越来越多的证据表明，铁在黑质（SN）中的积累与帕金森病（PD）的病理有关。二价金属转运蛋白 1（DMT1）是亚铁的内源性转运蛋白，其在 PD 患者死后的 SN 中的水平显著增加。为了研究 DMT1 基因与 PD 发生的可能关联，我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法在 192 名汉族 PD 患者和 193 名健康对照中研究了 DMT1 基因中的一个突变（1303C/A）和两个单核苷酸多态性（SNPs）（1254T/C 和 IVS4+44C/A）。对 10%的样本进行直接测序以验证基因分型结果。我们的结果未能发现测试的基因型、等位基因或突变与 PD 之间存在任何显著关联，然而，与对照组相比，PD 患者中出现了一种单倍型（1254T 和 IVS4+44C/A 多态性的 C 等位基因）的频率更高（18.2%比 11.4%，OR=1.72，95%CI=1.15-2.59，P=0.01）。这些结果表明，DMT1 基因中的 CC 单倍型可能是汉族人群中 PD 的一个潜在风险因素。
