Department of Molecular Genetics, University of Lodz, Pomorska 141/143, Lodz, Poland.
Graefes Arch Clin Exp Ophthalmol. 2012 Jul;250(7):1057-65. doi: 10.1007/s00417-012-1966-z. Epub 2012 Feb 29.
Age-related macular degeneration (AMD) is an ocular disease affecting macula - the central part of the retina, resulting in the degeneration of photoreceptors and retinal epithelium and causing severe central vision impairment. The pathophysiology of the disease is not completely known, but a significant role is attributed to genetic factors. The contribution of oxidative stress in AMD as a trigger of the degenerative process is well-established. Iron ions may act as a source of reactive oxygen species; therefore, maintaining iron homeostasis is important for redox balance in the organism. Diversity in iron homeostasis genes may counterpart in unbalanced redox state, and thus be involved in AMD pathophysiology.
In this work, we searched for an association between some single nucleotide polymorphisms in the divalent metal transporter 1 (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and environmental factors and AMD. Genotyping was performed using the PCR-RFLP method. DNA was obtained from 436 AMD patients and 168 controls.
We did not find any association between the genotypes of the two polymorphisms and AMD occurrence. However, we observed that AMD patients living in a rural environment and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk of AMD, while individuals with the CA genotype or the A allele had a decreased risk of the disease. Moreover, in male AMD patients the C allele increased the risk of the disease, while the AA genotype decreased it.
These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of AMD.
年龄相关性黄斑变性（AMD）是一种影响黄斑的眼部疾病 - 视网膜的中心部分，导致光感受器和视网膜上皮的退化，并导致严重的中心视力损害。该疾病的病理生理学尚不完全清楚，但遗传因素起着重要作用。氧化应激在 AMD 中作为退行性过程的触发因素的作用得到了很好的确立。铁离子可能作为活性氧的来源；因此，维持铁的动态平衡对于生物体的氧化还原平衡很重要。铁动态平衡基因的多样性可能与不平衡的氧化还原状态相对应，因此可能参与 AMD 的病理生理学。
在这项工作中，我们搜索了二价金属转运蛋白 1（DMT1）基因内含子 IVS4+44C>A（rs224589）和 3'-UTR c.2044T>C（rs2285230）的一些单核苷酸多态性与 AMD 之间的关联以及环境因素。使用 PCR-RFLP 方法进行基因分型。从 436 名 AMD 患者和 168 名对照中获得 DNA。
我们没有发现这两个多态性的基因型与 AMD 发生之间存在任何关联。然而，我们观察到生活在农村环境中的 AMD 患者并且 IVS4+44C>A 多态性的 CC 基因型具有增加的 AMD 风险，而具有 CA 基因型或 A 等位基因的个体具有降低的疾病风险。此外，在男性 AMD 患者中，C 等位基因增加了疾病的风险，而 AA 基因型则降低了风险。
这些结果表明，DMT1 基因的 VS4+44C>A 多态性可能与居住地点和性别相互作用，调节 AMD 的风险。
