Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Ophthalmology. 2012 Sep;119(9):1819-25. doi: 10.1016/j.ophtha.2012.02.044. Epub 2012 May 12.
PURPOSE: To assess the association between the genetic variants associated with the optic nerve vertical cup-to-disc ratio (VCDR) and the phenotypic features in patients with primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: Japanese patients with NTG (n = 213) and HTG (n = 212) and 191 control subjects without glaucoma. METHODS: DNA samples were genotyped for 7 single nucleotide polymorphisms (SNPs) associated with VCDR: rs1063192 (near gene: CDKN2B), rs10483727 (SIX1), rs17146964 (SCYL1), rs1547014 (CHEK2), rs1900004 (ATOH7), rs1926320 (DCLK1), and rs12015126 (RERE). MAIN OUTCOME MEASURES: The VCDR was compared between genotypes, and allele frequency differences were compared between NTG or HTG subjects and control subjects. Demographic and clinical features were compared between alleles in patients with NTG or HTG. RESULTS: There were significant VCDR differences (P = 0.0077 and P = 0.019) between the genotypes for rs1063192 (CDKN2B) and rs1547014 (CHEK2), respectively. There were significant differences in the rs1063192 (CDKN2B) and rs1900004 (ATOH7) allele frequencies between the NTG subjects and control subjects (P = 0.0023 and P = 0.028, respectively) and a significant difference (P = 0.013) in the rs1547014 (CHEK2) allele frequencies between the HTG subjects and control subjects. Ages at diagnosis were significantly different in the NTG subjects with and without the rs10483727 (SIX1) C allele (P = 0.017) or the rs1926320 (DCLK1) T allele (P = 0.040). Likewise, the age at diagnosis was significantly different (P = 0.037) in the HTG subjects with and without the rs12025126 (RERE) T allele. There were no significant associations between the maximum intraocular pressure (IOP) and 7 genotyped SNP alleles in patients with NTG or HTG. CONCLUSIONS: The rs1063192 (CDKN2B) and rs1900004 (ATOH7) seem to be non-IOP-related genetic risk factors for NTG, and the rs1547014 (CHEK2) is a genetic risk factor for HTG. Although the rs10483727 (SIX1), rs1926320 (DCLK1), or rs12025126 (RERE) alone may not be sufficient for the development of POAG, the association of these SNPs with a phenotypic feature in patients with NTG or HTG suggests that these loci contribute to the pathogenesis of POAG.
目的：评估与视神经垂直杯盘比（VCDR）相关的遗传变异与原发性开角型青光眼（POAG）患者表型特征之间的关联，包括正常眼压青光眼（NTG）和高眼压青光眼（HTG）。
设计：病例对照研究。
参与者和对照：日本 NTG（n=213）和 HTG（n=212）患者以及 191 名无青光眼对照受试者。
方法：对与 VCDR 相关的 7 个单核苷酸多态性（SNP）rs1063192（附近基因：CDKN2B）、rs10483727（SIX1）、rs17146964（SCYL1）、rs1547014（CHEK2）、rs1900004（ATOH7）、rs1926320（DCLK1）和 rs12015126（RERE）进行 DNA 分型。
主要观察指标：比较基因型之间的 VCDR，比较 NTG 或 HTG 受试者与对照受试者之间的等位基因频率差异。比较 NTG 或 HTG 患者中等位基因的人口统计学和临床特征。
结果：rs1063192（CDKN2B）和 rs1547014（CHEK2）基因型之间存在显著的 VCDR 差异（P=0.0077 和 P=0.019）。rs1063192（CDKN2B）和 rs1900004（ATOH7）等位基因频率在 NTG 受试者和对照受试者之间存在显著差异（P=0.0023 和 P=0.028），rs1547014（CHEK2）等位基因频率在 HTG 受试者和对照受试者之间也存在显著差异（P=0.013）。NTG 患者中 rs10483727（SIX1）C 等位基因（P=0.017）或 rs1926320（DCLK1）T 等位基因（P=0.040）的诊断年龄存在显著差异。同样，HTG 患者中 rs12025126（RERE）T 等位基因（P=0.037）的诊断年龄也存在显著差异。NTG 或 HTG 患者的最大眼内压（IOP）与 7 个基因分型 SNP 等位基因之间无显著相关性。
结论：rs1063192（CDKN2B）和 rs1900004（ATOH7）似乎是 NTG 与 IOP 无关的遗传风险因素，rs1547014（CHEK2）是 HTG 的遗传风险因素。尽管 rs10483727（SIX1）、rs1926320（DCLK1）或 rs12025126（RERE）单独可能不足以导致 POAG 的发生，但这些 SNP 与 NTG 或 HTG 患者表型特征的关联表明这些位点可能与 POAG 的发病机制有关。
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