Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.

Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.
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DOI:
10.1167/iovs.09-3688
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发表时间:
2009-12
影响因子:
4.4
通讯作者:
Tuo J
Tuo J
中科院分区:
医学2区
文献类型:
--
作者:
Cho Y;Wang JJ;Chew EY;Ferris FL 3rd;Mitchell P;Chan CC;Tuo J

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先天免疫似乎在年龄相关性黄斑变性(AMD)中起关键作用。尽管之前的两项研究报道了Toll样受体(TLR)-3和-4的基因变异与AMD相关,但其他研究尚未证实这些关联。在该研究中,使用三个独立的样品(两个基于美国临床的病例对照研究样品和一个基于澳大利亚人群的研究样品)来进一步评估TLR 3中的多态性rs3775291和TLR 4中的多态性rs 4986790与AMD的关联。AMD病例和无关对照组来自国家眼科研究所临床中心(NEI,n = 320)、AMD相关眼病研究(AREDS,n = 483)和蓝山眼科研究(BMES,n = 852)。从受试者中提取的DNA进行rs3775291和rs 4986790基因分型,并研究与AMD的关联。两个多态性rs3775291和rs 4986790在三个样本组中的任何一个或三个样本组的组合中与AMD都没有统计学显著相关性。对NEI、AREDS和BMES样本集中地图状萎缩或新生血管性AMD病例的分析也未能证明这两种单核苷酸多态性与晚期AMD的统计学显著相关性。即使使用先前验证的样本集和足够的研究功效,结果也没有证实在三个独立样本中单独或组合的TLR 3 rs3775291和TLR 4 rs 4986790与AMD的相关性。
Innate immunity appears to play a key role in age-related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case– control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 and rs4986790 in TLR4 with AMD. AMD cases and unrelated controls were collected from the National Eye Institute Clinical Center (NEI, n = 320), the Age-Related Eye Disease Study (AREDS, n = 483), and the Blue Mountains Eye Study (BMES, n = 852). DNA extracted from subjects was genotyped for rs3775291 and rs4986790, and the associations with AMD were investigated. Neither of the two polymorphisms rs3775291 and rs4986790 had a statistically significant association with AMD in any of the three sample sets or in combinations of the sets. Analysis of the combined geographic atrophy or neovascular AMD cases in the NEI, AREDS, and BMES sample sets also failed to demonstrate statistically significant associations of those two single nucleotide polymorphisms with advanced AMD. Even with previously verified samples sets and adequate study powers, the results did not confirm the reported associations of TLR3 rs3775291 and TLR4 rs4986790 with AMD in the three independent samples, individually or combined.
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