Impact of Tumor Necrosis Factor Receptor 1 (TNFR1) Polymorphism on Dry Eye Disease
Kelly Acuna, Anjalee Choudhary, Daniel Rodriguez, Anat Galor
Department of Ophthalmology, Miami VA Medical Center, Miami, Florida; Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami Florida
Purpose: Dry eye (DE) is a multifactorial disease with numerous presenting phenotypes and potential contributors. In order to deliver precision medicine, a better understanding of an individual’s contributors to disease is needed. Genetic polymorphisms have previously been shown to influence disease presentation and course in diseases relevant to DE, such as chronic pain syndromes. However, the impact of genetic polymorphisms on DE presentation and treatment response has not been well characterized. A previous study examined the effect of rs1800693 (chr12, alleles: T/C), a single nucleotide polymorphism (SNP) within the tumor necrosis factor receptor 1 (TNFR1) gene. Individuals with DE and homozygous alternate CC alleles were found to have a better symptomatic response to OCS-02 (a topical TNFα antibody) than those with TC or TT alleles. Building on this data, in the current study, we examine the frequency of a CC genotype in a novel population, South Florida veterans, and investigate whether the presence of this genotype impacts disease phenotype and response to anti-inflammatory therapy.
Methods: Prospective study of 328 individuals with a variety of DE symptoms and signs who underwent genetic profiling for rs1800693 (TT, TC, CC). The frequency of genotype CC was examined, as were relationships between genotype and phenotype and response to an anti-inflammatory agent.
Results: The mean age of the population was 61.7±9.8 years. 92% self-identified as male, 56% as white, and 21% as Hispanic. 13% (n=42) of individuals had a CC genotype, which was equally distributed between races but was less common in Hispanics. The presence of a CC genotype (as compared to TT and TC) did not influence the DE phenotype with similar DE symptoms and signs between the groups. In all, 30 individuals (4 with CC) were treated with an anti-inflammatory eyedrop. There was a trend for individuals with CC genotype to have a partial or complete response to treatment compared to the other two groups (100% vs. 38.5%, p=0.07).
Conclusions: The presence of homozygosity of risk allele C (CC genotype) in an SNP within TNFR1 was noted in a minority of individuals with various aspects of DE. However, this genotype did not relate to DE phenotype but did impact treatment response. These findings suggest that the current phenotyping strategies for DE are insufficient to identify underlying disease contributors, including potential genetic contributors.
Support: Supported by unrestricted grant from Oculis. Other support: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences R&D I01 CX002015 (Galor), Biomedical Laboratory R&D Service I01 BX004893 (Galor), Rehabilitation R&D I21 RX003883 (Felix), Department of Defense Vision Research Program W81XWH-20-1-0820 (Galor), Department of Defense Gulf War Illness Research Program W81XWH-20-1-0579 (Galor), National Eye Institute R01EY026174 (Galor) and R61EY032468 (Galor), NIH Center Core Grant P30EY014801 (institutional) and Research to Prevent Blindness Unrestricted Grant GR004596 (institutional).