Genetic Insights into Keratoconus Susceptibility: Unraveling the Interplay of Inflammation and Genomic Variants within the Iranian Population
Farideh Doroodgar, MD, MPH, FICO1 *, Sana Niazi, MD, MPH1 , Fatemeh Alizadeh, Ph.D2 , Seyedeh Maryam Razavi, M.Sc2 , Nazanin Jalilian, Ph.D3 , Asaad Azarnezhad, Ph.D4 , Feizollah Niazi, MD, MPH5 , Mohammad Ali Javadi, MD, PhD6 , Hamidreza Nematy, M.Sc7
- Translational Ophthalmology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Negah Aref Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
- Department of Genomic Psychiatry and Behavioural Genomics (DGPBG), Roozbeh Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Faculty Member, Clinical Research Development Center, Shahid Modarres Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Research Center, Labbafinezhad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Biomechanical Engineering, College of Engineering, University of Tehran, Tehran, Iran
Abstract: The primary objective of this investigation was to examine the potential correlation between variations within the interleukin-1 (IL-1) gene cluster and the predisposition to keratoconus (KC) within the Iranian population. Keratoconus, characterized by progressive corneal thinning and distortion, is a significant ocular concern with a global prevalence, underscoring its importance in the realm of eye health and the need for comprehensive research and management strategies.
Methods: In this investigation, individuals exhibiting clinical indications suggestive of mild forms of keratoconus (KC) were identified, a diagnosis established through both clinical observations and imaging techniques. The reference group consisted exclusively of individuals devoid of any personal or familial medical background pertaining to ocular, metabolic, or immune system disorders. Employing the established salting-out extraction method, genomic DNA was extracted from leukocytes present in peripheral blood. Genotypic assessments were conducted through agarose gel electrophoresis for IL1RN VNTR 86 bp and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques for rs16944 and rs1143634.
Results: The findings demonstrated a noteworthy correlation between the IL-1? rs1143634 and IL-1RN 86bp VNTR polymorphisms and the predisposition to keratoconus (KC) within the Iranian population. Marked distinctions in genotype distributions of rs1143634 and rs2234663 were observed between the case and control groups, with specific genotypes exhibiting a protective influence against KC. Logistic regression analysis unveiled a protective effect associated with the IL-1RN L allele and particular haplotypes against the development of KC. Conversely, no statistically significant association was discerned for the IL-1? rs16944 polymorphism.
Conclusion: This investigation furnishes substantiation for a correlation between variations within the IL-1 gene cluster and the predisposition to keratoconus (KC) in the Iranian populace. Subsequent studies involving larger and more heterogeneous cohorts are essential to corroborate these observations and delve into the underlying mechanisms at play.
