The aim of this study was to investigate the association of five polymorphisms in the IL1A and IL1B genes in Brazilian patients with primary open angle glaucoma (POAG). A case–control study, including 214 unrelated POAG patients and 187 healthy individuals, was conducted to evaluate the frequency of polymorphisms in the IL1A and IL1B genes. Ophthalmic evaluation was performed and genomic DNA was obtained from all participants. Five single nucleotide polymorphisms (SNPs): IL1A (–889C/T: rs1800587:C > T, +4845G/T:rs17561G>T) and IL1B (–31C/T:rs1143627:T > C, –511C/T:rs16944C>T and +3954C/T:rs1143634:C > T) were genotyped through direct sequencing. The association of individual SNPs was tested using logistic regression. There was an association between the –31C/T and –511 C/T polymorphisms in the IL1B gene with POAG (p = 0.002 and p = 0.009, respectively). High linkage disequilibrium was observed between the –31C/T and –511C/T polymorphisms. The statistical analysis showed that the T/C haplotype (–31/–511) in the IL1B gene is more frequent in controls (p = 0.011) and the C/T haplotype (–31/–511) is more common in POAG patients (p = 0.018). Among POAG cases, the genotypic distribution of the –31C/T and –511 C/T SNPs was significantly different in patients who underwent anti-glaucomatous surgery compared to patients without surgery (p = 0.016 and 0.023, respectively). There was no statistically significant difference for the remaining SNPs between POAG patients and controls. In conclusion, the C allele of the –31C/T and the T allele of the –511C/T polymorphisms in the IL1B gene may represent a “risk haplotype” for the development of POAG in Brazilian individuals. Further studies with larger cohorts of patients are necessary to substantiate these findings. Impact statement This study is the first, according to our knowledge, to show the association between glaucoma and the functional –31C/T single nucleotide polymorphism. We provide evidence indicating that homozygotes CC at –31C/T and TT at –511 C/T of IL1B are at risk for glaucoma. We also demonstrated that these polymorphisms are in strong linkage disequilibrium (LD). Increasing evidence support the role of inflammation in glaucoma and this study is an important result that reinforces these findings. How IL-1 signaling influences the triggering and pathogenesis of glaucoma remains to be investigated. Greater understanding of the mechanisms leading to glaucoma will provide the development of new management strategies that target the primary disease lesion and maybe the discovery of new treatments.
Investigation of ARHGEF12 Single Nucleotide Polymorphism in Hypercholesterolemia and Primary Open Angle Glaucoma
