Genetic Variants Associated With Different Risks for High Tension Glaucoma and Normal Tension Glaucoma in a Chinese Population
Genetic Variants Associated With Different Risks for High Tension Glaucoma and Normal Tension Glaucoma in a Chinese Population
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与中国人群患高压性青光眼和正常眼压性青光眼不同风险相关的基因变异。
DOI：
10.1167/iovs.14-16269
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Sun, Xinghuai
中科院分区：
文献类型：
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作者：
Chen, Yuhong;Hughes, Guy;Sun, Xinghuai
目的.我们调查了中国汉族人群中原发性开角型青光眼（POAG），包括高眼压性青光眼（HTG）和正常眼压性青光眼（NTG）与遗传因素的关系。我们收集了1157例POAG患者，其中HTG 860例，NTG 297例，以及934例正常对照。共13个先前报道的单核苷酸多态性（SNPs）位于4个基因区域（TMCO 1，CDKN 2B-AS 1，ATOH 7和SIX 1/SIX 6）进行基因分型。比较病例组和对照组以及HTG和NTG亚组的等位基因频率分布。眼压，垂直杯盘比（VCDR），中央角膜厚度（CCT），眼轴长度（AL），并在诊断时的年龄也进行了研究，这些SNP的基因型作为定量表型。TMCO 1位点的rs 4656461和rs7555523、CDKN 2B-AS 1位点的rs 523096和rs 2157719以及SIX 1/SIX 6位点的rs33912345和rs 10483727与POAG有统计学意义的相关性。在我们的数据集中，ATOH 7处的SNP与POAG没有显示出统计学显着相关性。在HTG和NTG的亚组分析中，CDKN 2B-AS 1和SIX 1/SIX 6处的多个变异体显示与NTG的关联性强于HTG。发现CDKN 2B-AS 1处的SNP rs 523096和rs 2157719以及SIX 1/SIX 6处的rs33912345和rs 10483727与IOP相关，其中次要等位基因与IOP升高相关。与此相反，TMC 0 1的SNP仅与HTG显著相关。中国汉族人群中CDKN 2B-AS 1、SIX 1/SIX 6和TMCO 1基因变异与原发性开角型青光眼相关基因CDKN 2B-AS 1和SIX 1/SIX 6似乎具有低眼压的POAG倾向，而TMCO 1风险等位基因携带者似乎倾向于发展高眼压的POAG。
PURPOSE. We investigated the association of genetic factors with primary open angle glaucoma (POAG), including high tension glaucoma (HTG) and normal tension glaucoma (NTG), in a Han Chinese population.METHODS. We recruited 1157 POAG cases, including 860 HTG and 297 NTG, and 934 normal controls. A total of 13 previously reported single nucleotide polymorphisms (SNPs) located at four gene regions (TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) was genotyped. Distributions of allele frequencies were compared between cases and controls as well as in the HTG and NTG subgroups. The IOP, vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT), axial length (AL), and age at diagnosis also were investigated as quantitative phenotypes with genotypes of these SNPs.RESULTS. The SNPs rs4656461 and rs7555523 at TMCO1, rs523096 and rs2157719 at CDKN2B-AS1, as well as rs33912345 and rs10483727 at SIX1/SIX6 showed statistically significant association with POAG. The SNPs at ATOH7 did not show statistically significant association with POAG in our dataset. In the subgroup analysis of HTG and NTG, multiple variants at CDKN2B-AS1 and SIX1/SIX6 showed stronger association with NTG than HTG. The SNPs rs523096 and rs2157719 at CDKN2B-AS1 as well as rs33912345 and rs10483727 at SIX1/SIX6 were found to be associated with IOP where the minor alleles were associated with an increase in IOP. In contrast, SNPs at TMCO1 showed significant association with HTG only.CONCLUSIONS. Genetic variants in CDKN2B-AS1, SIX1/SIX6, and TMCO1 were associated with POAG in a Han Chinese population. Genes CDKN2B-AS1 and SIX1/SIX6 seem to harbor a tendency toward POAG with lower IOP, while carriers of risk alleles at TMCO1 seem to be predisposed to developing POAG with higher IOP.