Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Department of Surgery, Tulane University, School of Medicine, New Orleans, LA.
Cornea. 2021 Jan;40(1):88-98. doi: 10.1097/ICO.0000000000002489.
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).
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.
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.
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.
首次研究角膜胶原交联（CXL）中核黄素和紫外线 A 治疗反应与胶原蛋白 COL4A3（rs55703767）、COL5A1（rs7044529）和 COL4A4（rs2229813）变体之间的关联在圆锥角膜（KC）患者中。
使用实时 TaqMan 聚合酶链反应对 147 名符合条件的 KC 患者进行指定胶原蛋白变体的基因分型。应用调整后的优势比（OR）和 95%置信区间（CI）来评估与 CXL 反应的关联强度，以降低最大角膜曲率和/或增加角膜厚度。
82 名患者（55.8%）CXL 后结果成功。总体分析显示，COL4A3、COL5A1 和 COL4A4 变体的次要等位基因频率分别为 0.22、0.22 和 0.38。成功组（43%）COL4A3 变体的 G/T 基因型比失败组（23%）更为常见（P<0.001）。杂合子（OR：2.19，95%CI，1.04-4.59，P<0.001）和超显性（OR：2.59，95%CI，1.25-5.38，P=0.008）模型下 COL4A3（rs55703767）与良好反应相关。相比之下，COL5A1 和 COL4A4 变体与 CXL 治疗后的有效反应无关。有趣的是，按性别分层分析显示，CXL 在 KC 女性患者中更为成功杂合子（OR：4.71，95%CI，1.74-12.75）、显性（OR：3.16，95%CI，1.29-7.78）和超显性（OR：5.18，95%CI，1.92-13.95）模型下 COL4A3（rs55703767）变体。
除其他研究变体外，COL4A3（rs55703767）变体可能与研究人群中 KC 患者的 CXL 核黄素/紫外线 A 治疗反应有关。需要在不同种族群体中进行大规模复制和随访研究。
