The Role of C21orf91 in Herpes Simplex Virus Keratitis

Background and Objectives: This paper aims to describe the single nucleotide polymorphisms (SNPs) of C21orf91 rs1062202 and rs10446073 in patients with herpetic keratitis by evaluating corneal sub-basal nerves, as well as the density of Langerhans cells (LC) and endothelium cells (EC) during the acute phase of the disease. Materials and Methods: A prospective clinical study included 260 subjects: 70 with herpetic eye disease, 101 with previous history of herpes labialis—but no history of herpetic eye disease—and 89 with no history of any herpes simplex virus (HSV) diseases. All subjects underwent a complete ophthalmological examination including in vivo laser scanning confocal microscopy (LSCM) of the central cornea. C21orf91 rs1062202 and rs10446073 were genotyped using the real-time polymerase chain reaction (PCR) method with the Rotor-Gene Q real-time PCR quantification system. SNPs were determined using TaqMan genotyping assay, according to the manufacturer’s manual. Results: The C21orf91 rs10446073 genotype GT was more frequent in the HSV keratitis group, compared with healthy controls (20.0% vs. 7.9%), OR 2.929[1.11–7.716] (p < 0.05). The rs10446073 genotype TT was more frequent in healthy controls (12.4% vs. 1.4%), OR 22.0[2.344–260.48] (p < 0.05). The rs10446073 genotype GT increased the risk of EC density being less than 2551.5 cell/mm(2), OR 2.852[1.248–6.515] (p < 0.05). None of the SNPs and their genotypes influenced the LC density and corneal sub-basal nerve parameters (p > 0.05). Conclusions: Our study reports a new association between herpetic keratitis and human gene C21orf91, with the rs10446073 genotype GT being more common in herpetic keratitis patients and increasing the risk for the disease by a factor of 2.9.