Tianjin Medical University, Tianjin, China.
PLoS One. 2012;7(8):e42387. doi: 10.1371/journal.pone.0042387. Epub 2012 Aug 3.
Genetic polymorphisms of the Optic atrophy 1 gene have been implicated in altering the risk of primary open angle glaucoma (POAG), especially the susceptibility to normal tension glaucoma (NTG), but the results remain controversial.
Multiple electronic databases (up to January 20, 2012) were searched independently by two investigators. A meta-analysis was performed on the association between Optic atrophy 1 polymorphisms (rs 166850 and rs 10451941) and normal tension glaucoma (NTG)/high tension glaucoma (HTG). Summary odds ratios (ORs) and 95% confidence intervals (CI) were estimated.
Seven studies of 713 cases and 964 controls for NTG and five studies of 1200 cases and 971 controls for HTG on IVS8+4C>T (rs 166850) and IVS8+32T>C (rs10451941) were identified. There were significant associations between the OPA1 rs10451941polymorphism and NTG susceptibility for all genetic models(C vs. T OR = 1.26, 95% CI 1.09-1.47, p = 0.002; CC vs. TT: OR = 1.52, 95% CI 1.04-2.20, p = 0.029; CC vs. CT+TT: OR = 1.64, 95% CI 1.16-2.33, p = 0.005; CC+CT vs. TT: OR = 1.21, 95% CI 1.02-1.44, p = 0.032). However, no evidence of associations was detected between the OPA1 IVS8+32C>T polymorphism and POAG susceptibility to HTG. Similarly, clear associations between the rs 166850 variant and NTG were observed in allelic and dominant models (T vs. C OR = 1.52, 95% CI 1.16-1.99, p = 0.002; TT+TC vs. CC OR = 1.50, 95% CI 1.13-2.01, p = 0.006) but not to HTG. In subgroup analyses by ethnicity, we detected an association between both OPA1 polymorphisms and risk for NTG in Caucasians but not in Asians. By contrast, no significant findings were noted between OPA1 variants for HTG, either in Caucasians or in Asians.
Both the IVS8+4C>T and IVS8+32T>C variants may affect individual susceptibility to NTG. Moreover, stratified analyses for NTG detecting the effects of both OPA1 polymorphisms seemed to vary with ethnicity. Further investigations are needed to validate the association.
视蛋白 1 基因的遗传多态性与原发性开角型青光眼（POAG）的风险改变有关，尤其是与正常眼压性青光眼（NTG）的易感性有关，但结果仍存在争议。
两位研究者分别独立检索了多个电子数据库（截至 2012 年 1 月 20 日）。对 Optic atrophy 1 基因多态性（rs166850 和 rs10451941）与正常眼压青光眼（NTG）/高眼压青光眼（HTG）之间的关联进行了荟萃分析。估计了综合优势比（OR）和 95%置信区间（CI）。
共纳入 7 项针对 NTG 的病例对照研究（713 例病例和 964 例对照）和 5 项针对 HTG 的病例对照研究（1200 例病例和 971 例对照），研究内容分别为 IVS8+4C>T（rs166850）和 IVS8+32T>C（rs10451941）。所有遗传模型（C 对 T OR=1.26，95%CI 1.09-1.47，p=0.002；CC 对 TT：OR=1.52，95%CI 1.04-2.20，p=0.029；CC 对 CT+TT：OR=1.64，95%CI 1.16-2.33，p=0.005；CC+CT 对 TT：OR=1.21，95%CI 1.02-1.44，p=0.032）中，OPA1 rs10451941 多态性与 NTG 易感性存在显著相关性。然而，OPA1 IVS8+32C>T 多态性与 POAG 易感性 HTG 之间没有发现关联。同样，在等位基因和显性模型中（T 对 C OR=1.52，95%CI 1.16-1.99，p=0.002；TT+TC 对 CC OR=1.50，95%CI 1.13-2.01，p=0.006），OPA1 变体与 NTG 存在明显相关性，但与 HTG 无相关性。按种族亚组分析，我们在高加索人群中发现了两种 OPA1 多态性与 NTG 风险之间的关联，但在亚洲人群中未发现。相反，无论是在高加索人还是亚洲人中，OPA1 变体与 HTG 之间均未发现有统计学意义的结果。
IVS8+4C>T 和 IVS8+32T>C 变异可能影响个体患 NTG 的易感性。此外，检测两种 OPA1 多态性对 NTG 影响的分层分析似乎与种族有关。需要进一步的研究来验证这种关联。
