Association of TGFB -509C>T promoter polymorphism with primary angle closure glaucoma in a North Indian Punjabi cohort

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

doi:10.1186/s12886-021-01924-4

Nanamika Thakur, Rashim Mannan + Show 3 more

Open Access

https://doi.org/10.1186/s12886-021-01924-4

Copy DOI

Abstract

PurposeTransforming growth factor beta (TGFB) is an important candidate gene implicated in glaucoma pathogenesis because it affects retinal ganglionic cell survival. The present study assessed the genetic association of -509C > T variant in the TGFB promoter region with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in a North Indian Punjabi population.MethodA total of 867 subjects (307 POAG, 133 PACG cases and 427 controls) were recruited from the targeted population. Genotyping was done by PCR-RFLP method and the data was analyzed using PLINK software (v1.07). Logistic regression under different genetic models was applied and genotype phenotype correlation was assessed by one-way ANOVA.ResultA statistically significant difference in the frequency of heterozygotes among PACG cases (53.16%) and controls (30.07%) (p = 0.0002) was observed. Genetic model analysis revealed that mutant “TT” genotype conferred 2-fold risk towards PACG development under recessive model (p = 0.0019) while dominant model and co-dominant model provided 0.62 and 0.37 fold protection against PACG (p = 0.025 and p = 0.0001, respectively). Data segregation based on sex revealed a strong protective effect of heterozygous ‘CT’ genotype against progression of PACG among females (p = 0.002, OR = 0.37, 95% CI = 0.19–0.70), but conferred 2.14-fold risk among female POAG subjects (p = 0.013).ConclusionThe study revealed a strong genetic association of -509C > T variant in TGFB with PACG in females. There is a need to replicate the results in a larger PACG cohort in other populations and further assess the contribution of sex specific factors in modifying genetic susceptibility to PACG.

Highlights

Glaucoma is a group of optic neuropathies with multifactorial etiology [1]
There is a need to replicate the results in a larger primary angle closure glaucoma (PACG) cohort in other populations and further assess the contribution of sex specific factors in modifying genetic susceptibility to PACG
transforming growth factor beta (TGFB) mediate excess extracellular (ECM) deposition to induce fibrosis [11] and since in glaucoma extensive ECM remodeling occurs in trabecular meshwork (TM) and ocular nerve head (ONH), dysfunctional TGFB signaling has been associated with glaucoma pathology [8, 12]

Summary

Introduction

Glaucoma is a group of optic neuropathies with multifactorial etiology [1]. Being the second leading cause of blindness worldwide, it is a serious health condition with high socio-economic impact. Sufficient evidence exist to suggest the involvement of chronic neuroinflammation due to altered levels of cytokines under glaucomatous stress conditions in contributing to RGCs death [4, 5]. Several ex-vivo and in-vitro studies have established that high TGFB level is one causative factor for elevated IOP and patients with increased levels of this cytokine in the aqueous humor (AH) are at a higher risk to develop elevated IOP [7,8,9]. In cultured human TM cells, exogenous TGFB treatment may increase the production of proteoglycans and other ECM proteins in these cells, which further reduce the outflow facility of the anterior chamber and contribute to increased IOP in the eye of glaucoma patients [13]. In the present study, association of the TGFB-1 -509C > T promoter polymorphism (rs1800469) with primary glaucoma (POAG/ PACG) was investigated in a North Indian Punjabi cohort

Methods

Results

Conclusion