Ahad Muhammad A, Missotten Tom, Abdallah Atiyeh, Lympany Penny A, Lightman Susan
Institute of Ophthalmology and Moorfields Eye Hospital, London UK.
Mol Vis. 2007 Mar 23;13:388-96.
Chemokines are important inflammatory mediators that play a crucial role in uveitis. Polymorphisms in chemokine genes can alter the expression of these genes in the inflammatory cells, which, in turn, can affect the clinical phenotype of the disease. The purpose of this study was to identify polymorphisms in chemokine genes that can predict visual outcome in patients with immune-mediated posterior segment uveitis.
This is a case-control study of 141 Caucasians with idiopathic immune-mediated posterior segment uveitis and 282 controls matched by age and ethnicity. Six polymorphisms in four genes, (MCP-1-2518A/G, RANTES-403G/A, RANTES-28C/G, CCR2 V64I, CCR5-59029G/A, and CCR5 32 bp deletion) were analyzed by sequence specific primers polymerase chain reaction.
Patients with G allele at MCP-1-2581 developed the disease at an early age as compared to patients with A allele corrected p value pc=0.003. Also patients with A allele at RANTES-403 position developed less severe disease and had better visual outcome when compared with patients with G allele (pc=0.02) Final visual acuity after 18 months was better in patients with 32 bp deletion of the CCR5 gene and in patients with the CCR2 wild-type genotype pc=0.02 and pc=0.04, respectively. Patients with the CCR2 64I allele also had a higher risk of developing an elevated intraocular pressure as compared to patients with the wild-type genotype (pc=0.007).
Though the utility for prediction of disease susceptibility of the studied polymorphisms in chemokine genes is in general not robust, we have found that polymorphisms in chemokine genes can influence the outcome of patients with idiopathic immune-mediated posterior segment uveitis. These associations require further analysis in other groups of patients.
趋化因子是重要的炎症介质，在葡萄膜炎中起关键作用。趋化因子基因多态性可改变这些基因在炎症细胞中的表达，进而影响疾病的临床表型。本研究旨在确定趋化因子基因中的多态性，以预测免疫介导的后段葡萄膜炎患者的视力预后。
这是一项病例对照研究，纳入141例患有特发性免疫介导的后段葡萄膜炎的白种人患者以及282例年龄和种族匹配的对照。采用序列特异性引物聚合酶链反应分析四个基因中的六个多态性（MCP-1-2518A/G、RANTES-403G/A、RANTES-28C/G、CCR2 V64I、CCR5-59029G/A和CCR5 32 bp缺失）。
与携带A等位基因的患者相比，携带MCP-1-2581 G等位基因的患者发病年龄较早（校正P值pc=0.003）。此外，与携带G等位基因的患者相比，RANTES-403位点携带A等位基因的患者疾病严重程度较低，视力预后较好（pc=0.02）。CCR5基因32 bp缺失的患者和CCR2野生型基因型的患者在18个月后的最终视力较好，校正P值分别为pc=0.02和pc=0.04。与野生型基因型的患者相比，携带CCR2 64I等位基因的患者发生眼压升高的风险也更高（pc=0.007）。
虽然趋化因子基因中所研究的多态性对疾病易感性的预测作用总体上并不显著，但我们发现趋化因子基因多态性可影响特发性免疫介导的后段葡萄膜炎患者的预后。这些关联需要在其他患者群体中进一步分析。
