Genetic association of IL1B gene variants with primary glaucoma in a North Indian Punjabi cohort: An original study and meta-analysis

Nanamika Thakur; Rajeev Kumar Pandey; Rashim Mannan; Archna Pruthi; Sanjana Mehrotra

doi:10.1016/j.exer.2023.109720

Genetic association of IL1B gene variants with primary glaucoma in a North Indian Punjabi cohort: An original study and meta-analysis

Exp Eye Res. 2024 Jan:238:109720. doi: 10.1016/j.exer.2023.109720. Epub 2023 Nov 11.

Authors

Nanamika Thakur¹, Rajeev Kumar Pandey², Rashim Mannan³, Archna Pruthi³, Sanjana Mehrotra⁴

Affiliations

¹ Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India; Department of Biotechnology, University Institute of Biotechnology, Chandigarh University, Mohali, Punjab, India.
² Thermo Fisher Scientific, Bengaluru, Karnataka, India.
³ All India Institute of Medical Sciences, New Delhi, India.
⁴ Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India. Electronic address: sanjana.bhu@gmail.com.

PMID: 37952723
DOI: 10.1016/j.exer.2023.109720

Abstract

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 I² 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_corr ₌ 0.011; OR = 0.55) and over dominant models (p = 0.010; OR = 0.59; p_corr ₌ 0.001; OR = 0.46). Significant association of +3953C > T was also observed with POAG under dominant (p = 0.011; OR = 1.46; p_corr ₌ 0.018; OR = 1.48) and PACG under recessive models (p < 0.0001; OR = 4.47; p_corr<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.

Keywords: Cytokines; Interleukin 1; Neurodegeneration; Primary angle closure glaucoma; Primary open angle glaucoma; Retinal ganglionic cells.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Genetic Predisposition to Disease
Glaucoma* / genetics
Glaucoma, Angle-Closure* / genetics
Glaucoma, Open-Angle* / genetics
Humans
Interleukin-1beta / genetics
Polymorphism, Single Nucleotide

Substances

IL1B protein, human
Interleukin-1beta