Abstract
Purpose: To investigate for the first time the association of collagen COL4A3 (rs55703767), COL5A1 (rs7044529), and COL4A4 (rs2229813) variants with response to corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A in patients with keratoconus (KC). Methods: A total of 147 eligible patients with KC were genotyped for the specified collagen variants using real-time TaqMan-based polymerase chain reaction. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with response to CXL for a decrease in maximum keratometry and/or an increase in corneal thickness. Results: Eighty-two patients (55.8%) had post-CXL successful outcomes. The overall analysis revealed that minor allele frequencies of COL4A3, COL5A1, and COL4A4 variants were 0.22, 0.22, and 0.38, respectively. The G/T genotype of the COL4A3 variant was more prevalent in the successful group (43%) compared with the failure group (23%) (P < 0.001). COL4A3 (rs55703767) was associated with a good response under heterozygote (OR: 2.19, 95% CI, 1.04-4.59, P < 0.001) and overdominant (OR: 2.59, 95% CI, 1.25-5.38, P = 0.008) models. By contrast, COL5A1 and COL4A4 variants were not associated with the effective response after CXL treatment. Interestingly, stratification analysis by sex revealed that CXL was more successful in female patients with KC under heterozygote (OR: 4.71, 95% CI, 1.74-12.75), dominant (OR: 3.16, 95% CI, 1.29-7.78), and overdominant (OR: 5.18, 95% CI, 1.92-13.95) models for COL4A3 (rs55703767) variant. Conclusions: The COL4A3 (rs55703767) variant, among other study variants, could be implicated in CXL riboflavin/ultraviolet A treatment response in patients with KC in the study population. Large-scale replication and follow-up studies in different ethnic groups are warranted.