Abstract
Long non-coding RNAs (lncRNAs) play essential roles in molecular diagnosis and therapeutic response in several diseases.
For the first time, we aimed to evaluate the association of four lncRNAs
(
(rs1061540T/C),
(rs3200401C/T), and
(rs12420823C/T) variants with susceptibility to diabetic retinopathy (DR), disease severity, and early therapeutic response to intravitreous anti-vascular endothelial growth factor aflibercept therapy.
This case-control study enrolled 126 adult patients with type 2 diabetes. TaqMan assays using Real-Time PCR were run for genotyping. Multivariable regression analyses were applied to assess the role of each polymorphism after the adjustment of covariates.
Carriers of
A/G and
T/C and C/C genotypes were more likely to develop DR [OR=3.15 (95% CI=1.15-8.64), and OR=4.31 (95% CI=1.78-10.47)], while
T/C conferred protection (OR=0.40, 95% CI=0.16-0.99). For
, and
genotype combinations, GTCT and GCCC had a higher disease risk (
=0.012). For disease severity,
T/T homozygosity was associated with higher DR grade [33.3% (T/T) vs 10% (C/C) and 4.2% (C/T) carriers,
=0.012]. Otherwise, patients with the
T variant exhibited better pre-treatment best-corrected visual acuity level (
=0.021). Following aflibercept administration, carrying the
A or
T/C was associated with a poor therapeutic response (OR=5.02, 95% CI=1.60-15.76, and OR=10.23, 95% CI=1.51-69.15, respectively).
The lncRNAs
(
and
(rs1061540T/C) were associated with increased DR susceptibility and poor response to aflibercept treatment, while
(rs3200401C/T) conferred protection to DR. These genetic determinants could be useful in DR risk stratification and pharmacogenetics after validation in large-scale studies.