原发性开角型青光眼患者小梁网糖皮质激素诱导反应蛋白和视神经病变诱导反应蛋白基因多态性的研究

目的 探讨小梁网糖皮质激素诱导反应蛋白（MYOC）和视神经病变诱导反应蛋白（OPTN）基因的单核苷酸多态性（SNP）及其与正常眼压性青光眼（NTG）和高眼压性青光眼（HTG）发病的关系。方法应用聚合酶链反应（PCR）扩增全基因组DNA，用构像敏感性凝胶电泳（CSGE）和荧光标记自动DNA测序法筛选和鉴定94例HTG，48例NTG和77名正常对照的MYOC基因和OPTN基因的SNP。结果共检测出14个MYOC基因序列改变，5个为新序列改变（V53A，I304I，T347T，1-126T〉C和IVS2＋172C〉A）。其中V53A错义突变首次在POAG中发现；1-83G〉A通常与R76K伴随出现；各SNP的等位基因及基因型在HTG，NTG与对照组问差异无统计学意义（P〉0．05）。对OPTN基因，共检测出12个SNP，3个为新序列改变（V161M，I407T和L211L），其中I407T和L211L仅在HTG患者中检测到。此外，同义突变T34T在NTG患者中，其等位基因和基因型频率与对照组相比，差异均有统计学意义（P=0．001和0．004）；而在HTG患者中，只有等位基因频率与对照组相比，差异有统计学意义（P=0．044）。位于内含子区域的序列改变IVS8＋20G〉A，其等位基因和基因型频率在HTG、NTG与对照组之间，差异均有统计学意义（P=0．016和0．014；P=0．027和0．026）。结论MYOC和OPTN基因多态性可能与中国人的POAG发病相关，不引起氨基酸改变的基因序列改变在POAG致病中可能起一定的作用。

Polymorphisms of myocilin and optineurin in primary open angle glaucoma patients

Objective To detect the single nucleotide polymorphisms (SNPs) of the myocilin (MYOC) and optineurin (OPTN) genes, and to investigate their associations with high tension glaucoma (HTG) and normal tension glaucoma (NTG). Methods SNPs were detected using polymerase chain reaction (PCR), followed by conformation sensitive gel electrophoresis (CSGE) and fluorescent labeling automated DNA sequencing among 94 unrelated patients with HTG, 48 unrelated patients with NTG, and 77 unrelated control subjects. Results Fourteen MYOC sequence alterations were identified, five of them: V53A, I304I, T347T, 1-126T>C, and IVS2+172C>A, were novel. Among them, V53A was for the first time found in primary open angle glaucoma (POAG) patient. R76K usually occurred with the promoter polymorphism 1-83G>A. No sequence alterations in the MYOC gene showed significant differences among the HTG, NTG and control subjects (all P>0.05). A total of 12 sequence alterations were identified in the OPTN gene, and three of them: V161M, I407T and L211L, were novel. Among them, I407T and L211L were found only in the HTG patients. The allele and genotype frequencies of T34T in the NTG patients were significantly higher than those of the controls (P=0.001 and 0.004 respectively). In HTG, only the allele frequency of T34T was 24% (23/96), significantly higher than those of the NTG group (16.5%, 31/188) and the control group (9.1%, 14/154) (both P<0.05). In addition, IVS8+20G>A was found only in the HTG (3.1%, 3/96) and NTG patients (3.7%, 7/188), and had significantly higher frequencies in the HTG and NTG patients when compared with the controls (P=0.016 and 0.014, and P=0.027 and 0.026). Conclusion Polymorphisms in the MYOC and OPTN genes are associated with POAG in Chinese people. Moreover, sequence alterations not causing amino acid changes may play a role in the pathogenesis of POAG.