Inflammatory and genomic interactions within keratoconus susceptible patients: a nationwide registered case-control study.

Purpose: This study aimed to investigate the association between variants in the interleukin (IL)-1 gene cluster and susceptibility to keratoconus (KC) in an Iranian population.

Methods: In the case group, there were 188 KC patients diagnosed by clinical findings and corneal tomography. The control group included all 205 healthy controls with no personal or family history of eye-related, metabolic, or immune system-related disease. Using the standard salting out extraction procedure, genomic DNA was isolated from peripheral blood leukocytes. The genotypes were determined by applying agarose gel electrophoresis for the IL-1RN 86 bp VNTR and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rs16944 and rs1143634.

Results: The results showed a significant association between the IL-1β rs1143634 (rs1143634 T allele, P = 0.008) and IL-1RN 86 bp VNTR polymorphisms (LL and LS genotype, P = 0.048 and 0.012 respectively) and susceptibility to KC in the Iranian population. The genotype distributions of rs1143634 (P = 0.004) and rs2234663 (P = 0.042) significantly differed between case and control groups, with certain genotypes demonstrating a protective effect against KC. Logistic regression analysis revealed a protective effect of the IL-1RN L allele [odds ratio (OR) = 0.367, 95% confidence interval (CI): 0.240-0.562; P = 0.000] and certain haplotypes (OR = 0.628, 95% CI: 0.447-0.884; P = 0.007) against KC. However, no significant association was found for the IL-1β rs16944 polymorphism.

Conclusion: This study provides evidence for an association between variants in the IL-1 gene cluster and susceptibility to KC in an Iranian population. Further research on larger and more diverse populations is warranted to validate these findings and explore the underlying mechanisms involved.