TY - JOUR
T1 - Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension
AU - Badrinarayanan, Lakshmi
AU - Chitipothu, Srujana
AU - Ramasubramanyan, Sharada
AU - Sripriya, Sarangapani
AU - Rishi, Pukhraj
AU - Rishi, Ekta
AU - George, Ronnie
AU - Lakshmi, Baddireddi Subhadra
AU - Elchuri, Sailaja V.
N1 - Publisher Copyright:
© 2020 International Journal of Ophthalmology (c/o Editorial Office). All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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 iPLEXTM 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% confidenceinterval 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 TAOHT 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.
AB - 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 iPLEXTM 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% confidenceinterval 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 TAOHT 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.
KW - Dexamethasone
KW - Diabetes
KW - Myopia
KW - Neurodegeneration
KW - Ocular hypertension
KW - Single nucleotide polymorphisms
KW - Triamcinolone-acetonide
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U2 - 10.18240/ijo.2020.08.17
DO - 10.18240/ijo.2020.08.17
M3 - Article
AN - SCOPUS:85091021108
SN - 2222-3959
VL - 45
SP - 1294
EP - 1305
JO - International Journal of Ophthalmology
JF - International Journal of Ophthalmology
IS - 6
ER -