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Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension.

AIM
To access the association of forty-eight single nucleotide polymorphisms (SNPs) identified from Caucasian population with steroid-induced ocular hypertension (OHT) in India population.


METHODS
Fifty-four triamcinolone-acetonide (TA) and forty-seven dexamethasone (Dex) administered subjects were enrolled in the study after a written consent. Intraocular pressure (IOP) values were recorded for a period of 6-month post steroid injections and patients were grouped as steroid-responders (SR: IOP≥21 mm Hg) and non-responders (NR: IOP≤20 mm Hg). Genomic DNA was isolated from peripheral venous blood. Forty-eight SNPs identified in TA treated Caucasian patients by genome wide association study (GWAS) were genotyped using iPLEX™ MassARRAY among TA as well as Dex administered Indian patients. Genotyping data of 48 general subjects from a previous study were considered as reference controls for statistical analysis. Genotypic frequencies were calculated and P-value, Chi-square and odds ratio at 95% confidence-interval of group A (steroid treated vs controls), group B (SR vs NR), group C (phenotype correlation: influence of time, severity and gender on IOP rise), were calculated. P<0.05 was considered to be statistically significant.


RESULTS
OHT was observed in 50% of TA and 26% of Dex administered patients, respectively. IOP rise was mostly severe (>30 mm Hg) and immediate (<1wk) among TA-SR patients while it was noticed to be mild (<30 mm Hg) and between 1-2mo among Dex-SR patients. Logistic regression for risk factor correlation with OHT remained non-significant, hence these factors were not considered as confounding parameters for further analysis. rs133, rs34016742, rs274554, rs10936746, rs274547, rs804854, rs7751500, rs359498, and rs7547448 SNPs significantly varied even after Bonferroni corrections (P<0.0025; group A). rs1879370 (TA) and rs6559662 (Dex) were significantly (P<0.05) associated with OHT (group B). rs133 (severe IOP rise), rs11047639 and rs1879370 (male gender), and rs11171569 (immediate IOP rise) significantly (P<0.05) influenced the phenotype correlation only among TA-OHT patients. However, the significance of these SNPs in group B and phenotype analysis (group C) was lost upon Bonferroni corrections (P<0.0025).


CONCLUSION
Prevalence of OHT in study population is observed to be similar to other studies both in TA and Dex treated patients. We can correlate rs34016742 involved in diabetes signaling pathway to the occurrence of ocular edematous and inflammatory conditions. Except rs133 that is involved in neuro-degeneration and myopia occurrence, none of the other SNPs identified in Caucasian population possess any correlation with OHT incidence in TA and Dex administered Indian subjects.