Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4110-6. doi: 10.1167/iovs.09-4974. Epub 2010 Mar 31.
To evaluate the variants of 10 genes for association with primary open-angle glaucoma (POAG) in a Chinese population.
A total of 405 unrelated patients with POAG (255 high-tension glaucoma [HTG], 100 normal-tension glaucoma [NTG], and 50 juvenile-onset open-angle glaucoma [JOAG]) and 201 control subjects were recruited. Seventeen variants in 10 genes with reported association with POAG were genotyped for analysis of allele and haplotype frequencies between cases and control subjects. These genes included CDH1 (cadherin 1, type 1, E-cadherin), CDKN1A (cyclin-dependent kinase inhibitor 1A), CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), GSTM1 (glutathione S-transferase mu 1), GSTT1 (glutathione S-transferase theta 1), MTHFR (5,10-methylenetetrahydrofolate reductase), NOS3 (nitric oxide synthase 3), OPA1 (optic atrophy 1), TNF (tumor necrosis factor), and TP53 (tumor protein p53).
One SNP (-308G>A; rs1800629) in TNF demonstrated a significant association with HTG (P = 0.012). The allele G frequency was higher in HTG patients than in control subjects (94.6% vs. 90.3%; OR = 1.89). One haplotype consisting of rs1799724 and rs1800629 was significantly associated with HTG (P = 0.015, corrected P = 0.045). One SNP (R72P; rs1042522) in TP53 was significantly associated with NTG (P = 0.018). The allele G frequency was higher in NTG patients than in control subjects (56.1% vs. 45.8%; OR = 1.52). The significance of these associations survived the Bonferroni correction (corrected P < 0.024). Other gene variants were not significantly associated with HTG (P > 0.063) or NTG (P > 0.13). None of the studied variants was significantly associated with JOAG (P > 0.17).
The findings suggest that variants in TNF and TP53 are risk factors for POAG, whereas variants in other studied genes are not major risk factors for POAG, at least in the Chinese population.
在中国人群中评估与原发性开角型青光眼（POAG）相关的 10 个基因的变异。
共招募了 405 名无关的 POAG 患者（255 名高眼压青光眼[HTG]，100 名正常眼压青光眼[NTG]和 50 名青少年开角型青光眼[JOAG]）和 201 名对照。对与 POAG 相关的 10 个基因中的 17 个变异进行基因分型，以分析病例和对照组之间的等位基因和单倍型频率。这些基因包括 CDH1（钙粘蛋白 1，类型 1，E-钙粘蛋白），CDKN1A（细胞周期蛋白依赖性激酶抑制剂 1A），CYP1B1（细胞色素 P450，家族 1，亚家族 B，多肽 1），GSTM1（谷胱甘肽 S-转移酶 mu 1），GSTT1（谷胱甘肽 S-转移酶 theta 1），MTHFR（5,10-亚甲基四氢叶酸还原酶），NOS3（一氧化氮合酶 3），OPA1（视神经萎缩 1），TNF（肿瘤坏死因子）和 TP53（肿瘤蛋白 p53）。
TNF 中的一个 SNP（-308G>A；rs1800629）与 HTG 显著相关（P=0.012）。HTG 患者的等位基因 G 频率高于对照组（94.6% vs. 90.3%；OR=1.89）。由 rs1799724 和 rs1800629 组成的一个单倍型与 HTG 显著相关（P=0.015，校正 P=0.045）。TP53 中的一个 SNP（R72P；rs1042522）与 NTG 显著相关（P=0.018）。NTG 患者的等位基因 G 频率高于对照组（56.1% vs. 45.8%；OR=1.52）。这些关联的意义在经过 Bonferroni 校正后仍然存在（校正 P<0.024）。其他基因变异与 HTG（P>0.063）或 NTG（P>0.13）均无显著关联。在所研究的变异中，没有一个与 JOAG 显著相关（P>0.17）。
这些发现表明，TNF 和 TP53 中的变异是 POAG 的危险因素，而其他研究基因中的变异不是 POAG 的主要危险因素，至少在中国人群中不是。
