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Shweta Paresh Kitchloo, Paul Gabriel, Manishi Desai, Haiyan Gong, Hyunjoo Jean Lee; Are Thrombospondin-1 SNPs associated with steroid response and expression levels in saliva?. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1012.
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Ophthalmic steroid use is a known risk factor for ocular hypertension and glaucoma. Thrombospondin-1 (THBS1/TSP-1) is a matricellular protein increased in the trabecular meshwork, and in response to steroids. TSP1-/- mice have lower intraocular pressure (IOP), and are protected from steroid-induced elevation of IOP. We aimed to investigate whether THBS1 SNPs are associated with IOP elevation in patients treated with ophthalmic steroids. Also, the C allele of THBS1r1478604 was previously found to be associated with decreased TSP-1 expression in peripheral blood and the ocular surface; we investigated whether the same might be true in saliva.
Adult subjects using topical ophthalmic steroids for reasons other than glaucoma surgery were recruited at Boston Medical Center with IRB approval. Steroid-responders (cases) were defined as IOP change ≥ 6 mmHg and IOP ≥ 24mmHg while using topical ophthalmic steroid. Steroid non-responders (controls) were defined as those who were on a significant dose of steroid (dexamethasone 0.1% ≥ TID, prednisolone 1% ≥ TID or difluprednate 0.05% ≥ QD) for at least 4 weeks and did not exhibit the aforementioned changes in IOP. Collected saliva was immediately stabilized in Qiagen AllProtect. DNA was isolated from cells. The frequency of alleles for TSP-1 SNPs 1-5 were determined. Concentration of TSP-1 was measured by ELISA.
Of 42 recruited subjects, 13 were excluded due to incomplete records. Of the 29 eligible subjects, 15 (52%) were steroid responders and 14 (42%) non-responders. There was no significant difference in race, ethnicity, age, and sex between groups. TSP-1 protein levels were not significantly different between steroid responders and non-responders (6.8 ± 5.7 vs. 8.3 ± 5.9, p= 0.5), but were significantly different by r1478604 genotype (5.4 ± 3.8 (CC) vs.10.5 ± 5.7 (CT) vs. 2.8 ± 3.6 (TT); p= 0.006) (Figure 1). We did not find any significant associations of THBS1 SNP genotypes with steroid response (Table 1).
There were significantly different levels of saliva TSP-1 protein in subjects with different THBS1 rs1478604 genotypes. However, the highest level was associated with heterozygotes. The biological explanation for this is unclear. Although there was no association found between THBS1 SNPs and steroid response, a larger sample size is warranted to confirm our findings.
This is a 2020 ARVO Annual Meeting abstract.
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