Background

IL6 is an important candidate gene implicated in the pathogenesis of glaucoma. The present study assessed the genetic association of −174G > C and −572G > C polymorphisms in the IL6 promoter region with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in a north Indian Punjabi cohort.

Methods

910 subjects (313 POAG, 148 PACG cases and 449 controls) were recruited. Genotyping was done by TaqMan assays. Genetic association was tested under different genetic models using Plink. Diplotype and linkage disequilibrium (LD) analysis was done through Haploview. Association of clinical parameters with the genotypes was assessed by one-way ANOVA. Adjustment for potential confounding variables was done by binary logistic regression. IL6 levels were measured in POAG patients and controls.

Results

572G > C variant showed marginal difference in genotype frequency between pooled cases and POAG subgroup with respect to controls (p = 0.042; OR = 1.33; and p = 0.041; OR = 1.37). The GC genotype conferred 1.37-fold protection under codominant model in POAG cases (p = 0.034, OR = 1.37, 95% CI = 1.02–1.85; p_corr = 0.025, OR = 1.45, 95% CI = 1.04–2.02). The mean value for IOP was elevated among cases having ‘CC’ genotype at the −572G > C locus (p = 0.037).

Lower levels of IL6 were detected in POAG patients in plasma samples (p = 0.0001).

Conclusion

The study reports suggestive evidence for −572G > C variant in IL6 in affecting genetic susceptibility to POAG in the targeted North Indian Punjabi cohort. A correlation of IL6 levels in aqueous humor (AH) and systemic circulation in POAG was observed, the functional and diagnostic relevance of which may be further investigated.

中文翻译：

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-572G > C 多态性与北印度旁遮普人群原发性开角型青光眼遗传关联的提示性证据

背景

IL6是参与青光眼发病机制的重要候选基因。本研究评估了北印度旁遮普队列中IL6启动子区域-174G > C 和 -572G > C 多态性与原发性开角型青光眼 (POAG) 和原发性闭角型青光眼 (PACG) 的遗传关联。

方法

招募了 910 名受试者（313 名 POAG、148 名 PACG 病例和 449 名对照）。通过 TaqMan 分析进行基因分型。使用 Plink 在不同的遗传模型下测试遗传关联。双倍型和连锁不平衡（LD）分析是通过Haploview完成的。通过单向方差分析评估临床参数与基因型的关联。通过二元逻辑回归对潜在的混杂变量进行调整。在 POAG 患者和对照中测量 IL6 水平。

结果

相对于对照组，572G > C 变体显示合并病例和 POAG 亚组之间的基因型频率存在微小差异（p = 0.042；OR = 1.33；和 p = 0.041；OR = 1.37）。在 POAG 病例中，GC 基因型在共显性模型下提供了 1.37 倍的保护（p = 0.034，OR = 1.37，95% CI = 1.02-1.85；p _corr  = 0.025，OR = 1.45，95% CI = 1.04-2.02）。在 -572G > C 基因座具有“CC”基因型的病例中，IOP 的平均值升高（p = 0.037）。

在 POAG 患者的血浆样本中检测到较低水平的 IL6（p = 0.0001）。

结论

该研究报告了IL6中-572G > C 变体影响目标北印度旁遮普人群对 POAG 遗传易感性的提示性证据。观察到房水 (AH) 中 IL6 水平与 POAG 体循环中的相关性，其功能和诊断相关性可以进一步研究。