Association of Common SIX6 Polymorphisms With Peripapillary Retinal Nerve Fiber Layer Thickness: The Singapore Chinese Eye Study
Association of Common SIX6 Polymorphisms With Peripapillary Retinal Nerve Fiber Layer Thickness: The Singapore Chinese Eye Study
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DOI：
10.1167/iovs.14-15863
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Wong, Tien Yin
中科院分区：
文献类型：
--
作者：
Cheng, Ching-Yu;Allingham, R. Rand;Wong, Tien Yin
目的.最近发现常见的SIX 6错义变体rs33912345与青光眼高度相关。本研究的目的是调查该SIX 6变异体和视乳头周围视网膜神经纤维层（RNFL）厚度之间的相关性，该厚度是在人群中通过光谱域光学相干断层扫描（SD-OCT）测量的。研究对象来自新加坡华人眼科研究（SCES），这是一项针对40岁或以上新加坡华人的基于人群的调查。受试者接受全面的眼部检查。使用频域OCT测量RNFL厚度。使用人外显子组珠芯片对SIX 6 rs33912345（Asn 141 His）进行基因分型。结果。分析纳入了来自1243例SCES受试者（平均年龄：55.0 ± 7.4岁）的总计2129只眼，这些受试者具有rs33912345基因型数据和SD-OCT图像。其中，21例受试者的26只眼患有青光眼。研究受试者中rs33912345风险变体C（His 141）的频率为80%。每个rs33912345 C等位基因与RNFL厚度减少1.44 μ m后，调整年龄，性别，遗传主成分，和轴长（P = 0.001）。在2096只非青光眼眼中，这些相关性保持相似，其中每个C等位基因与RNFL厚度减少1.39 μ m相关（P = 0.001）。在上级RNFL区观察到最强的相关性（每个危险等位基因减少2.83 μ m，P < 0.001），其次是下级RNFL区（每个危险等位基因减少2.24 μ m，P = 0.003），而鼻和颞区的相关性没有达到显著性。具有SIX 6错义变体的非青光眼个体在已知特别受青光眼影响的区域中RNFL厚度减少。这可能是携带SIX 6 His 141风险变异个体POAG风险增加的主要机制。
PURPOSE. Recently the common SIX6 missense variant rs33912345 was found to be highly associated with glaucoma. The aim of this study was to investigate the association between this SIX6 variant and peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) in a population setting.METHODS. Study subjects were enrolled from the Singapore Chinese Eye Study (SCES), a population-based survey of Singaporean Chinese aged 40 years or older. Subjects underwent a comprehensive ocular examination. Spectral-domain OCT was used to measure RNFL thicknesses. Genotyping of SIX6 rs33912345 (Asn141His) was performed using Human-Exome BeadChip.RESULTS. A total of 2129 eyes from 1243 SCES subjects (mean age: 55.0 +/- 7.4 years) with rs33912345 genotype data and SD-OCT images were included for the analysis. Of these, 26 eyes of 21 subjects had glaucoma. The frequency of rs33912345 risk variant C (His141) was 80% in the study subjects. Each rs33912345 C allele was associated with a decrease of 1.44 mu m in RNFL thickness after adjusting for age, sex, genetic principal components, and axial length (P = 0.001). These associations remained similar in 2096 nonglaucoma eyes in which each C allele was associated with a decrease of 1.39 mu m in RNFL thickness (P = 0.001). The strongest association was observed in the superior RNFL sector (a decrease of 2.83 mu m per risk allele, P < 0.001) followed by the inferior RNFL sector (a decrease of 2.24 mu m per risk allele, P = 0.003), while the association did not reach significance in the nasal and temporal sectors.CONCLUSIONS. Nonglaucomatous individuals with the SIX6 missense variant have reduced RNFL thickness in regions known to be particularly affected in those with glaucoma. This may be the primary mechanism for increased risk of POAG in individuals who carry the SIX6 His141 risk variant.