Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India; Department of Biotechnology, University Institute of Biotechnology, Chandigarh University, Mohali, Punjab, India.
Thermo Fisher Scientific, Bengaluru, Karnataka, India.
Exp Eye Res. 2024 Jan;238:109720. doi: 10.1016/j.exer.2023.109720. Epub 2023 Nov 11.
Interleukin (IL) 1B is an important candidate gene in glaucoma pathogenesis as it affects the survival of retinal ganglion cells (RGCs). In the present study, -511T/C and +3953C/T polymorphisms in the IL1B were assessed as genetic risk factors for primary open angle (POAG) and angle closure glaucoma (PACG) in a North Indian Punjabi cohort comprising 867 samples (POAG cases = 307; PACG cases = 133 and controls = 427). Genetic association, diplotype and linkage disequilibrium (LD) analyses were performed. Corrections for confounding variables and multiple testing were applied. An updated meta-analysis was also performed. Pooled OR with 95% CI was calculated for dominant, over dominant, and recessive models. Level of heterozygosity among studies was tested using I statistic with fixed or random effect model based on the extent of heterogeneity. For -511T > C polymorphism, a positive association was observed with PACG under dominant (p = 0.038; OR = 0.65; p 0.011; OR = 0.55) and over dominant models (p = 0.010; OR = 0.59; p 0.001; OR = 0.46). Significant association of +3953C > T was also observed with POAG under dominant (p = 0.011; OR = 1.46; p 0.018; OR = 1.48) and PACG under recessive models (p < 0.0001; OR = 4.47; p<0.0001; OR = 4.06). While C-C diplotype provided protection against primary glaucoma (0.67-fold; p = 0.0004), T-T and T-C diplotypes predisposed individuals to higher risk (1.31-fold; p = 0.030 and 1.36-fold; p = 0.022 respectively). In meta-analysis, a significant association between +3453 C>T and POAG was observed under dominant (pooled OR = 1.33, p = 0.0046) and over dominant (pooled OR = 1.25; p = 0.0269) models with overall heterogeneity of 15% and 0% respectively. The study provides strong evidence of IL1B variants in modifying genetic susceptibility to primary glaucoma in the targeted North Indian Punjabi population. Replication of the present findings in other populations, and functional studies are warranted to further assess the relevance of IL1B variants in the pathogenesis of primary glaucoma.
白细胞介素 (IL) 1B 是青光眼发病机制中的一个重要候选基因，因为它影响视网膜神经节细胞 (RGC) 的存活。在本研究中，评估了 IL1B 中的 -511T/C 和 +3953C/T 多态性作为印度北部旁遮普邦队列中原发性开角 (POAG) 和闭角型青光眼 (PACG) 的遗传风险因素，该队列包括 867 个样本 (POAG 病例=307; PACG 病例=133 和对照组=427)。进行了遗传关联、二倍型和连锁不平衡 (LD) 分析。应用了混杂变量和多重检验的校正。还进行了更新的荟萃分析。计算了显性、过显性和隐性模型的合并 OR 及其 95%CI。使用基于异质性程度的固定或随机效应模型，使用 I 统计量测试研究之间的杂合度水平。对于 -511T>C 多态性，在显性模型下观察到与 PACG 呈正相关 (p=0.038;OR=0.65;p<0.011;OR=0.55) 和过显性模型下 (p=0.010;OR=0.59;p<0.001;OR=0.46)。在 +3953C>T 多态性中也观察到与 POAG 呈显著关联显性模型下 (p=0.011;OR=1.46;p<0.018;OR=1.48) 和 PACG 下隐性模型下 (p<0.0001;OR=4.47;p<0.0001;OR=4.06)。C-C 二倍型为原发性青光眼提供了保护 (0.67 倍;p=0.0004)，而 T-T 和 T-C 二倍型使个体易患更高的风险 (1.31 倍;p=0.030 和 1.36 倍;p=0.022)。在荟萃分析中，在显性 (合并 OR=1.33，p=0.0046) 和过显性 (合并 OR=1.25;p=0.0269) 模型下，观察到 +3453C>T 与 POAG 之间存在显著关联，总体异质性分别为 15%和 0%。该研究为白细胞介素 1B 变异在调节目标印度北部旁遮普邦人群原发性青光眼遗传易感性方面提供了有力证据。在其他人群中复制本研究结果，并进行功能研究，以进一步评估白细胞介素 1B 变异在原发性青光眼发病机制中的相关性。
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