Cytokine Polymorphism in Noninfectious Uveitis
Cytokine Polymorphism in Noninfectious Uveitis
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DOI：
10.1167/iovs.09-4583
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发表时间：
2010-08-01
影响因子：
4.4
通讯作者：
Churchill, Amanda J.
中科院分区：
文献类型：
--
作者：
Atan, Denize;Fraser-Bell, Samantha;Churchill, Amanda J.
目的.非感染性葡萄膜炎是一种威胁视力的免疫介导的眼内炎症性疾病。葡萄膜炎在多个家族中的遗传及其与已知的单基因和多基因免疫疾病的相关性表明，常见的遗传变异是葡萄膜炎和其他免疫疾病易感性的基础。TNFA和IL 10是强有力的候选基因，考虑到这些细胞因子对炎症、免疫耐受和免疫排斥的影响。在英国和爱尔兰共和国的四个区域中心的192名葡萄膜炎患者和92名人群对照受试者中研究了跨越TNFA和IL 10基因组区域的12种多态性的作用。结果表明，葡萄膜炎与IL 10基因中的三种单倍型标记SNP（htSNP）相关：htSNP 2（rs6703630）、htSNP 5（rs 2222202）和htSNP 6（rs3024490）。IL 10 htSNP 2AG/htSNP 5 TC是最显著相关的单倍型（P = 0.00085），而LTA +252 AA/TNFhtSNP 2GG单倍型是保护性的（P = 0.00031）。此外，亚组分析显示，TNFd 4等位基因的频率在非缓解性眼病患者和/或需要更高水平维持免疫抑制的患者中更高。虽然这些关联在Bonferroni校正后失去了意义，但它们推断出的关系可能会被更大规模的研究所验证。由于这些变异与几种免疫疾病的易感性和严重程度有关，因此结果支持共同的遗传决定因素影响自身免疫的共同机制的假设。（Invest Ophthalmol维斯科学。2010;51：4133-4142）DOI：10.1167/iovs.094583
PURPOSE. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis.METHODS. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland.RESULTS. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA + 252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study.CONCLUSIONS. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity. (Invest Ophthalmol Vis Sci. 2010;51:4133-4142) DOI:10.1167/iovs.094583