Suggestive evidence of male specific genetic association of IL8 -251T>A promoter polymorphism with primary angle closure glaucoma in a north Indian Punjabi population.

Abstract

Background: Overproduction of IL-8 in the retina and optic nerve may affect the survival of retinal ganglion cells (RGCs) and contribute to axonal damage in glaucoma. The -251T > A functional variant in the promoter region of the IL8 gene is known to affect its transcriptional activity, as demonstrated in in vitro assays.

Methods: The present study investigates the genetic association of this polymorphism with primary glaucoma in a North Indian Punjabi cohort. A total of 226 primary open angle glaucoma (POAG), 132 primary angle closure glaucoma (PACG) patients and 424 matched controls were recruited. Genotyping was performed using the restriction length polymorphism (RFLP) method.

Results: Association analysis was done by PLINK software and appropriate corrections were applied for potential confounding variables. No significant differences in allele or genotype frequency were observed in pooled cases when compared to controls. However, after segregating the data into POAG and PACG and based on sex, significant difference was observed in the allele frequency among PACG males and control male subjects (p = 0.014, OR = 0.52, 95% CI = 0.31-0.88). The heterozygous 'AT' genotype provided 0.46 times protection for PACG among males (p = 0.028, OR = 0.46, 95% CI = 0.23-0.92). Genetic model analysis revealed that the combination of 'AT + AA' genotypes conferred protection against the development of PACG among male subjects under a dominant model (p = 0.013, OR = 0.44, 95% CI = 0.23-0.84; p_corr=0.003, OR = 0.30, 95% CI = 0.14-0.67).

Conclusions: This study suggests a genetic association of the -251T > A variant with PACG in males in the targeted population and highlights the importance of sex- specific analysis in glaucoma. The biological mechanisms underlying these differences should be further explored to better understand the observed sex bias in PACG.