Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma
Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma
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ABCA1 和 PMM2 附近的常见变异与原发性开角型青光眼相关
DOI：
10.1038/ng.3078
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发表时间：
2014-10-01
期刊：
影响因子：
30.8
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
--
作者：
Chen, Yuhong;Lin, Ying;Yang, Zhenglin
我们对1007例原发性开角型青光眼(POAG)合并高压青光眼的患者进行了全基因组关联研究，并与1009名来自中国南部的对照组进行了对照。我们观察到位于ABCA1附近的多个SNPs在9q31.1(rs2487032；P=1.66×10(-8))处与全基因组显著关联，并提示在16p13.2(rs3785176；P=3.18×10(-6))的PMM2中存在关联。我们在新加坡的525例HPG病例和912例对照中复制了这些发现，在中国的另一组1,374例POAG病例和4053例对照中重复了这些发现。我们观察到两个基因座上多个SNP与全基因组的显著关联(代表ABCA1的rs2487032的P=2.79×10(-19)和代表PMM2的rs3785176的P=5.77×10(-10))。ABCA1和PMM2在小梁网、视神经等眼组织中均有表达。此外，ABCA1在视网膜的神经节细胞层高度表达，这一发现与它在青光眼发展中的作用一致。
We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.