García Montserrat, Álvarez Lydia, Fernández Ángela, González-Iglesias Héctor, Escribano Julio, Fernández-Vega Beatriz, Villota Eva, Fernández-Vega Cueto Luis, Fernández-Vega Álvaro, Coca-Prados Miguel
a Fernández-Vega University Institute, Foundation of Ophthalmological Investigation, University of Oviedo , Oviedo , Spain.
b Department of Neurodegenerative Eye Disease , Fernández-Vega Ophthalmological Institute , Oviedo , Spain.
Ophthalmic Genet. 2017 Sep-Oct;38(5):451-458. doi: 10.1080/13816810.2017.1288825. Epub 2017 Mar 1.
To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD).
A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software.
The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed.
The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.
为阐明单核苷酸多态性（SNP）在西班牙北部年龄相关性黄斑变性（AMD）患者金属硫蛋白（MT）基因中的潜在作用。
一项病例对照研究纳入了130名确诊为AMD的西班牙北部无亲缘关系的本地人（46例干性、35例新生血管性和49例混合性）以及96名年龄和种族匹配的健康对照。从外周血中提取DNA，并使用TaqMan探针针对位于5个MT基因（MT1A：rs11076161、rs11640851、rs8052394和rs7196890；MT1B：rs8052334、rs964372和rs7191779；MT1M：rs2270836和rs9936741；MT2A：rs28366003、rs1610216、rs10636和rs1580833；MT3：rs45570941）的14个SNP进行基因分型。使用HaploView 4.0软件进行关联研究。
等位基因和基因型频率分析显示，MT2A基因的rs28366003与干性AMD显著相关。干性AMD中AG基因型的频率显著高于对照病例（p = 2.65×10；AG与AA相比），使干性AMD的风险增加了九倍多（OR = 9.39，95% CI：2.11 - 41.72），而AA基因型则具有疾病保护作用（OR = 0.82，95% CI：0.71 - 0.95）。在分析的其余14个SNP中，AMD患者与对照之间未观察到统计学上的显著差异。
本研究首次调查了MT基因SNP与AMD易感性之间的潜在关联。我们发现MT2A基因的SNP rs28366003与西班牙北部人群干性AMD的易感性显著相关。
