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.
Keywords: Case-control study; Genetic association study; Neurodegeneration; PACG; Polymorphism; Primary glaucoma; TGFB -509C > T.