Department of Ophthalmology, Yeditepe University Medical Faculty, Istanbul, Turkey.
Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4732-7. doi: 10.1167/iovs.09-4842. Epub 2010 Apr 7.
Oxidative stress seems to be an important factor in the development of age-related macular degeneration (AMD). The role of DNA repair mechanisms has also received attention recently in AMD pathogenesis. This case-control study was conducted to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD), codons 312 and 751, and x-ray cross-complementing group 1 (XRCC1), codons 194 and 399, in patients with AMD and in disease-free control subjects.
Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze XPD Asp312Asn and Lys751Gln and XRCC1 Arg194Trp and Arg399Gln in 120 patients with AMD (65 with dry type and 55 with wet type) and in age-matched 205 disease-free control subjects.
Genotypic and allelic distributions of the polymorphisms were detected. For the XPD polymorphism, although the allele frequencies were not different between the patients and healthy control subjects, there was a significant difference between frequencies for the XPD751 Gln/Gln genotype in AMD patients (9%) and healthy control subjects (19%; P=0.02). The XPD751 Gln/Gln genotype seemed to have a protective effect against development of AMD (odds ratio, 0.41; 95% confidence interval, 0.19-0.88). Stratification by subtype of AMD revealed that the XPD751 Gln/Gln genotype was significantly lower only in the patients with dry type (P=0.02). These interactions remained nearly significant after Bonferroni correction (P<0.0125). Haplotype analysis for the two XPD polymorphisms revealed that the haplotype GC (312Asp-(751)Gln) was a protective haplotype against AMD. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the XRCC1 gene between the patients and the control subjects.
Polymorphism in XPD codon 751 may be associated with the development of AMD.
氧化应激似乎是年龄相关性黄斑变性（AMD）发展的一个重要因素。DNA 修复机制在 AMD 发病机制中的作用最近也受到了关注。本病例对照研究旨在确定两种 DNA 修复酶基因，即着色性干皮病互补组 D（XPD）密码子 312 和 751 以及 X 射线交叉互补组 1（XRCC1）密码子 194 和 399 的多态性在 AMD 患者和无病对照中的频率。
采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析 120 例 AMD 患者（65 例干性，55 例湿性）和年龄匹配的 205 例无病对照中 XPD Asp312Asn 和 Lys751Gln 以及 XRCC1 Arg194Trp 和 Arg399Gln 的多态性。
检测到了多态性的基因型和等位基因分布。对于 XPD 多态性，尽管患者和健康对照组之间的等位基因频率没有差异，但 AMD 患者（9%）和健康对照组（19%；P=0.02）之间 XPD751 Gln/Gln 基因型的频率存在显著差异。XPD751 Gln/Gln 基因型似乎对 AMD 的发生有保护作用（比值比，0.41；95%置信区间，0.19-0.88）。按 AMD 亚型分层显示，仅在干性 AMD 患者中 XPD751 Gln/Gln 基因型显著降低（P=0.02）。在 Bonferroni 校正后，这些相互作用仍接近显著（P<0.0125）。对两个 XPD 多态性的单体型分析表明，单体型 GC（312Asp-（751）Gln）是 AMD 的保护性单体型。患者和对照组之间 XRCC1 基因多态性的基因型和等位基因分布无统计学差异。
XPD 密码子 751 多态性可能与 AMD 的发生有关。
