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

• Main Authors: Nanamika Thakur, Rajeev Kumar Pandey, Rashim Mannan, Archna Pruthi, Sanjana Mehrotra
• Format: Article
• Language: English
• Published: BMC 2021-04-01
• Series: BMC Ophthalmology
• Subjects: Primary glaucoma; Case-control study; Genetic association study; TGFB -509C > T; Polymorphism; Neurodegeneration
• Online Access: https://doi.org/10.1186/s12886-021-01924-4

Abstract Purpose Transforming 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. Method A 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. Result A 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). Conclusion The 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.