Purpose

AMD genetic studies have revealed various genetic loci as causal to AMD pathology. We have described the genetic complexity of Indian AMD by describing the interaction of genotypes and subsequent changes in protein expression under the influence of environmental factors. This can be utilized to enhance the diagnostic and therapeutic efficacy in AMD patients.

Design

Genotype association was studied in 464 participants (AMD =277 & controls = 187) for eight genetic variants and their corresponding protein expression

Methods

SNP analysis and protein expression analysis was carried out in AMD and controls in tandem with longitudinal assessment of protein levels during the course of AMD pathology. ANCOVA and contrast analysis were used to examine the genotypic interactions and corresponding alterations in protein levels. In order to identify the important genetic variants Logistic Regression (LR) modeling was carried out and to authenticate the model Area under the Receiver Operating Characteristic curve (AUROC) were also computed.

Results

We have found genetic variants of rs5749482 (TIMP-3), rs11200638 (HTRA1), rs769449 (APOE) and rs6795735 (ADAMTS9) to be associated with AMD, concomitant with significant alterations of studied proteins levels. Analysis also revealed that the genetic interaction between APOE-HTRA1 genotypes and changes in LIPC levels (>6 pg/ug) by one unit change in SNP, play a crucial role in AMD. LR model suggested that the seven factors (including both genetic and environmental) can be utilized to predict the AMD cases with 88% efficacy and 95.6% AUROC.

Conclusion

Results suggest that diagnostic and therapeutic strategy for Indian AMD must include estimation of genetic interaction and concomitant changes in expression levels of proteins under influence of environmental factors.

中文翻译：

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基因网络决定了 AMD 的易感性

目的

AMD 基因研究揭示了各种基因位点是 AMD 病理学的原因。我们通过描述基因型的相互作用和随后在环境因素影响下蛋白质表达的变化来描述印度 AMD 的遗传复杂性。这可用于增强 AMD 患者的诊断和治疗功效。

设计

在 464 名参与者（AMD = 277 和对照组 = 187）中研究了八种遗传变异及其相应的蛋白质表达的基因型关联

方法

在 AMD 和对照中进行 SNP 分析和蛋白质表达分析，同时纵向评估 AMD 病理学过程中的蛋白质水平。ANCOVA 和对比分析用于检查基因型相互作用和蛋白质水平的相应变化。为了识别重要的遗传变异，进行了逻辑回归 (LR) 建模，并计算了接收者操作特征曲线 (AUROC) 下的模型面积。

结果

我们发现 rs5749482 (TIMP-3)、rs11200638 (HTRA1)、rs769449 (APOE) 和 rs6795735 (ADAMTS9) 的遗传变异与 AMD 相关，伴随着研究蛋白质水平的显着变化。分析还表明，APOE-HTRA1 基因型之间的遗传相互作用和 LIPC 水平的变化（>6 pg/ug）在 SNP 的一个单位变化中起着至关重要的作用。LR 模型表明，7 个因素（包括遗传和环境）可用于预测 AMD 病例，有效率为 88%，AUROC 为 95.6%。

结论

结果表明，印度 AMD 的诊断和治疗策略必须包括在环境因素影响下估计遗传相互作用和蛋白质表达水平的伴随变化。