Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Exp Eye Res. 2012 May;98:58-66. doi: 10.1016/j.exer.2012.02.008. Epub 2012 Mar 26.
Age-Related Macular Degeneration (AMD) is an eye disease that results in progressive and irreversible loss of central vision and is considered as the primary cause of visual impairment, including blindness, in the elderly in industrialized countries. Oxidative stress has been implicated in the pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the repair of oxidatively damaged DNA in the base excision repair pathway. The DNA glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine, respectively. Our study was designed to examine the association between the c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism (rs3219489) of the MUTYH gene and AMD as well as the modulation of this association by some clinical and lifestyle factors. Genotypes were determined in DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form of the disease and 105 sex- and age-matched individuals without AMD. We observed an association between AMD, dry and wet forms of AMD and the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004; 0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003; 0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we detected were driven by the dry AMD. We observed some statistically significant association between the occurrence of AMD and its dry and wet forms and genotypes of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline character of all this association we do not consider them as medically relevant. Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with dry AMD. Further studies are needed to determine possible association between AMD and the c.972G>C-MUTYH polymorphism.
年龄相关性黄斑变性（AMD）是一种眼部疾病，可导致中央视力进行性和不可逆转的丧失，是导致工业化国家老年人视力损害甚至失明的主要原因。氧化应激与 AMD 的发病机制有关。hOGG1 和 MUTYH 基因在碱基切除修复途径中对氧化损伤 DNA 的修复中发挥重要作用。hOGG1 和 MUTYH 基因编码的 DNA 糖苷酶通过识别和去除分别与 8-氧鸟嘌呤和腺嘌呤配对的 8-氧鸟嘌呤来启动该途径。我们的研究旨在研究 hOGG1 基因的 c.977C>G 多态性（rs1052133）和 MUTYH 基因的 c.972G>C 多态性（rs3219489）与 AMD 之间的关系，以及一些临床和生活方式因素对这种关联的调节作用。我们在 271 名 AMD 患者（包括 101 名湿性和 170 名干性疾病患者）和 105 名性别和年龄匹配的无 AMD 个体的血液 DNA 中确定了基因型。我们观察到 AMD、干性和湿性 AMD 与 c.977C>G-hOGG1 多态性的 C/G 基因型和 G 等位基因之间存在关联（p0.006；0.009；0.021 和 0.004；0.005；0.016）。另一方面，C/C 基因型和 C 等位基因降低了 AMD 以及其干性或湿性形式的发病风险（p0.002；0.003；0.010 和 0.004；0.005；0.016）。因此，我们检测到的关联是由干性 AMD 驱动的。我们观察到 AMD 及其干性和湿性形式的发生与另一种多态性 c.972G>C-MUTYH 多态性的基因型之间存在一些统计学上显著的关联，但由于所有这些关联的边界特征，我们不认为它们具有医学相关性。我们的研究结果表明，c.977C>G-hOGG1 多态性可能与干性 AMD 有关。需要进一步的研究来确定 AMD 与 c.972G>C-MUTYH 多态性之间的可能关联。
